Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done.
Adoption of single-fraction lung stereotactic body radiation therapy (SBRT) for patients with medically inoperable early stage non-small-cell lung cancer (NSCLC) or oligometastatic lung disease, even during the coronavirus disease 2019 (COVID-19) pandemic, was limited despite encouraging phase II trial results. Barriers to using single-fraction SBRT may include lack of familiarity with the regimen and lack of clarity about the expected toxicity. To address these concerns, we performed a systematic review of prospective literature on single-fraction SBRT for definitive treatment of early stage and oligometastatic lung cancer. A PubMed search of prospective studies in English on single-fraction lung SBRT was conducted. A systematic review was performed of the studies that reported clinical outcomes of single-fraction SBRT in the treatment of early stage non-small-cell lung cancer and lung oligometastases. The current prospective literature including nine trials supports the use of single-fraction SBRT in the definitive treatment of early stage peripheral NSCLC and lung oligometastases. Most studies cite local control rates of >90%, mild toxicity profiles, and favorable survival outcomes. Most toxicities reported were grade 1-2, with grade ≥3 toxicity in 0-17% of patients. Prospective trial results suggest potential consideration of utilizing single-fraction SBRT beyond the COVID-19 pandemic.


Effect of opioids on delayed neuronal death in the gerbil hippocampus.
The effect of opioids on delayed neuronal death was evaluated in the gerbil hippocampus. Male Mongolian gerbils were subjected to transient forebrain ischemia and neuronal density was evaluated in the hippocampus 7 days following ischemia. When hypothermia during and after ischemia was prevented, treatment with morphine, U-50488H, or naloxone provided no significant protection. In contrast, a spontaneous drop in rectal temperature to 32 degrees C at the end of ischemia produced near-complete protection of CA1 pyramidal neurons. No opioids modulate the protective effect of hypothermia.


Molecular characterization of immune responses of Helicoverpa armigera to infection with the mermithid nematode Ovomermis sinensis.
Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.


Description of the Pupa of Culicoides crucifer Clastrier (Diptera: Ceratopogonidae).
The pupa of Culicoides crucifer Clastrier is described, illustrated and photomicrographed by using binocular microscope and phase-contrast microscopy from material collected in an artificial container in Manaus, Brazil. The pupa shows features typical of pupae occurring in calm and clean waters, and it is compared with its similar congeners of the subgenus Haematomyiidium, Culicoides annuliductus Wirth and Culicoides debilipalpis Lutz.


Device-associated infections in neonatal care units in a middle-income country, 2016-2018.
Describe the device-associated infections in the NICUs in Cali - Colombia, a middle-income country, between August 2016 to December 2018. Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR CI95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53-8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33-7.06, p = 0.008). These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.


Investigation of carbonic anhydrase inhibitory potency of (Z/E)-alkyl N'-benzyl-N-(arylsulfonyl)-carbamimidothioates.
Aim: Among 15 human (h) carbonic anhydrase (CA; EC 22.214.171.124) isoforms, two (hCA IX and XII) play important roles in the growth and survival of tumor cells, making them therapeutic targets for cancer treatment. This study aimed to develop novel sulfonamide-based compounds as selective hCA IX and XII inhibitors. Materials & methods: A library of novel N-sulfonyl carbamimidothioates was obtained for CA inhibitory activity studies against four hCA isoforms. Results: None of the developed compounds displayed inhibitory potential against off-target isoforms hCA I and II. However, they effectively inhibited tumor-associated hCA IX and XII. Conclusion: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity.


Transthyretin cardiac amyloidosis in patients after TAVR: clinical and echocardiographic findings and long term survival.
The aim of this study was to examine the prevalence of amyloid transthyretin (ATTR) cardiac amyloidosis in patients 1-2 years after trans-catheter aortic valve replacement (TAVR) and to assess their clinical and echocardiographic outcome and long-term survival. We enrolled 88 patients, mean age 81 years, 534 (390-711) days after TAVR. Patients underwent a Tc99m-PYP scintigraphy for the diagnosis of ATTR cardiac amyloidosis. Eleven (12.5%) participants were diagnosed with ATTR cardiac amyloidosis. Eighty eight per cent of patients without amyloidosis were in New York Heart Association Classes 1-2 after TAVR, compared with 64% patients with ATTR cardiac amyloidosis (P = 0.022). There were no differences in left ventricular (LV) ejection fraction (P = 0.69) between patients with and without ATTR cardiac amyloidosis at enrolment. The LV mass index and pulmonary artery pressure were significantly higher in patients with ATTR cardiac amyloidosis (P = 0.046 and P = 0.002, respectively). Global longitudinal strain and myocardial work efficiency were significantly lower in patients with ATTR cardiac amyloidosis (P = 0.031 and P = 0.048, respectively). We assessed changes in echocardiographic data, from the time of TAVR to enrolment, and as expected, there was a significant decrease in aortic valve gradient in both groups. There was a significant reduction in LV mass and LV mass index and improvement in basal segment LV strain in the ATTR cardiac amyloidosis negative group (P = 0.045, P = 0.046 and 0.023, respectively). However, in the ATTR cardiac amyloidosis group the change in LV mass and LV mass index and LV basal strain values was not significant (P = 0.24, P = 0.13 and P = 0.35, respectively). The were no significant changes in other echocardiographic parameters in both groups. The patients were followed for 1150 (1086-1221) days after enrolment. Twenty seven patients had at least one cardiac hospitalization during of follow up, of them seven were with ATTR cardiac amyloidosis and 20 patients without amyloidosis (P = 0.017). Eighteen patients (20%) died during follow up; 12 (14%) patients died due to cardiac causes. There was no difference in all-cause and cardiac mortality between patients with and without ATTR cardiac amyloidosis (P = 0.6 and P = 0.53, respectively). The long-term survival after TAVR is not significantly affected by the presence of ATTR cardiac amyloidosis. However, the clinical course of these patients and the LV hemodynamic improvement is less favourable. This hypothesis-generating study suggests screening for ATTR cardiac amyloidosis in patients who underwent TAVR and have limited clinical or echocardiographic improvement, because they may potentially improve with new therapies for ATTR cardiac amyolidosis.


[Triiodothyronine receptors (TR) are present in breast cancer tissues].
Possible relationships between breast cancer and thyroid hormones have been suggested for many years. The aim of this study was qualitative examination of triiodothyronine receptors (TR) in breast cancer tissues and in non cancerous breast tissue taken from the opposite side to the localization of the tumor. The material consisted of 15 breast cancer tissues of grades G1 to G3 and the same number of control tissues obtained during radical mastectomy or local tumor resection. Tissues were homogenized. Protein fraction was isolated. Protein for TR was assessed in Western Blot reaction. Protein fraction for TR was present in all cancer tissues and 6 healthy controls. Obtained data may suggest so far unknown role of thyroid hormones and their nuclear receptors in the generation and development of breast cancer.


A study of margin width and local recurrence in breast conserving therapy for invasive breast cancer.
Debate continues on what is an adequate margin width to define a clear margin and whether there is a need to excise pectoral fascia or remove skin in breast conserving surgery. This study set out to provide answers to these questions. 1411 patients with invasive breast cancer were treated by breast conserving surgery and post-operative whole breast radiotherapy from January 2000 to December 2005. Distance from each margin to any in situ or invasive cancer was measured and recorded. If full thickness of breast tissue was removed no re excision of anterior and posterior margins was performed even if disease was <1 mm from a margin. Patients ≤50 years of age and those with anterior or posterior margins <1 mm to invasive cancer had a radiation boost. Median follow-up time was 6.4 years. Local in breast tumour relapse (IBTR) occurred in 50 patients. The overall actuarial IBTR rate at 5 years was 2.2%. There was no difference in IBTR when comparing patients with radial margins of 1-5 mm or 5-10 mm. Anterior and posterior margins <1 mm or with ink on tumour cells were not associated with an increase in IBTR. There is no justification for radial margins of greater than 1 mm. If the anterior or posterior margin is <1 mm and full thickness of breast tissue has been removed, then re excision of these margins is unnecessary if boost radiotherapy is delivered.


Human interferon: mass production in a newly established cell line, MG-63.
MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid.polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.


Syntheses, crystal structures and Hirshfeld surface analyses of four mol-ecular salts of amitriptynol.
The syntheses and crystal structures of four salts of amitriptynol (C20H25NO) with different carb-oxy-lic acids are described. The salts formed directly from solutions of amitriptyline (which first hydrolysed to amitriptynol) and the cor-responding acid in aceto-nitrile to form amitriptynolium [sys-tem-atic name: (3-{2-hy-droxy-tri-cy-clo[9.4.0.03,8]penta-deca-1(11),3,5,7,12,14-hexa-en-2-yl}pro-pyl)di-methyl-az-an-ium] 4-meth-oxy-benzoate monohydrate, C20H26NO+·C8H7O3 -·H2O, (I), ami-triptynolium 3,4-di-meth-oxy-benzoate trihydrate, C20H26NO+·C9H9O4 -·3H2O, (II), amitriptynolium 2-chloro-benzoate, C20H26NO+·C7H4ClO2 -, (III), and amitriptynolium thio-phene-2-carboxyl-ate monohydrate, C20H26NO+·C5H3O2S-·H2O, (IV). Compound (III) crystallizes with two cations, two anions and six water mol-ecules in the asymmetric unit. The different conformations of the amitriptynolium cations are determined by the torsion angles in the di-methyl-amino-propyl chains and the -CH2-CH2- bridge between the benzene rings in the tricyclic ring system, and are complicated by disorder of the bridging unit in II and III. The packing in all four salts is dominated by N-H⋯O and O-H⋯O hydrogen bonds. Hirshfeld surface analyses show that the amitriptynolium cations make similar inter-species contacts, despite the distinctly different packing in each salt.


Clinical, genetic, and molecular characterization of hyperphosphatasia with mental retardation: a case report and literature review.
Hyperphosphatasia with mental retardation syndrome (HPMRS) is a recessive disorder characterized by high blood levels of alkaline phosphatase together with typical dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and developmental delay. Genes involved in the glycosylphosphatidylinositol pathway and known to be mutated in HPMRS have never been characterized in the Lebanese population. Herein, we describe a pair of monozygotic twins presenting with severe intellectual disability, distinct facial dysmorphism, developmental delay, and increased alkaline phosphatase level. Two individuals underwent whole exome sequencing followed by Sanger sequencing to confirm the co-segregation of the mutation in the consanguineous family. A biallelic loss of function mutation in PGAP3 was detected. Both patients were homozygous for the c.203delC (p.C68LfsX88) mutation and the parents were carriers confirming the founder effect of the mutation. High ALP serum levels confirmed the molecular diagnosis. Our findings have illustrated the genomic profile of PGAP3-related HPMRS which is essential for targeted molecular and genetic testing. Moreover, we found previously unreported clinical findings such as hypodontia and skin hyperpigmentation. These features, together with the novel mutation expand the phenotypic and genotypic spectrum of this rare recessive disorder.


The adolescent as forgiver.
A social cognitive developmental model of forgiveness is described and tested in two studies, the second being a replication of the first. In study 1, 59 subjects in grades 4, 7, 10, college and in adulthood were given a forgiveness interview that assessed six stages of forgiveness development, Rest's DIT measure of justice development, and a religiosity scale. As predicted, there were strong age trends for forgiveness and justice. Both forgiveness and justice were related but distinct constructs. The more one practiced one's faith, the higher one was in forgiveness stage. Study 2, with 60 subjects, replicated the above findings. The studies give strong evidence that people's understanding of forgiveness develops with age. Implications for adolescent development are drawn.


Sustained cell body reactivity and loss of NeuN in a subset of axotomized bulbospinal neurons after a chronic high cervical spinal cord injury.
Following central nervous system lesion, the ability of injured axons to regrowth may depend on the level and duration of the injured cell body response (CBR). Therefore, to investigate whether axotomized brainstem neurons maintain a durable growth-competent state after spinal cord injury, we studied the effect of a chronic C2 hemisection in rats on the expression of various CBR markers involved in axon regeneration, such as c-Jun, ATF-3, HSP27, NO synthase (NOS), and also of the neural mature phenotype marker NeuN, in the bulbospinal respiratory neurons as compared to the gigantocellularis nucleus. Both at 7 and 30 days post-lesion (DPL), c-Jun and HSP27 were present in, respectively, ~60 and ~20% of the axotomized respiratory neurons, whereas the apoptotic factor caspase 3 was not detected in these cells. NOS appeared belatedly, and it was detected in ~20% of the axotomized respiratory neurons at 30DPL. At 30DPL, these different CBR markers were strongly colocalized in a sub-population of axotomized respiratory neurons and also in a sub-population of injured neurons within the gigantocellularis nucleus. Such CBR was also accompanied by a sustained alteration of the neural mature phenotype, as indicated by a loss of NeuN immunoreactivity selectively in HSP27+ bulbospinal neurons at 7DPL and 30DPL. Altogether, this study shows that a subset of axotomized medullary respiratory neurons remains in a growth-competent state after a chronic injury, suggesting that they may play a preferential role in long-lasting respiratory neuroplasticity processes.


Intracarotid infusion of PCNU (NSC: 95466): preclinical toxicological study in dogs.
The prognosis of patients with unresectable intracerebral primary and metastatic tumours that recur following cranial irradiation is poor. Chemotherapy agents have been of limited value. PCNU--a new nitrosourea, has been shown to have the optimum log P for treatment of murine intracerebral tumours. We conducted a preclinical toxicological study of intracarotid injection of PCNU in dogs. Our results show that there was no major neurological or retinal toxicity from the drug, suggesting that PCNU may be less toxic than the presently available BCNU.


AAV4-mediated expression of IGF-1 and VEGF within cellular components of the ventricular system improves survival outcome in familial ALS mice.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron cell death in the cortex, brainstem, and spinal cord. Extensive efforts have been made to develop trophic factor-based therapies to enhance motor neuron survival; however, achievement of adequate therapeutic delivery to all regions of the corticospinal tract has remained a significant challenge. Here, we show that adeno-associated virus serotype 4 (AAV4)-mediated expression of insulin-like growth factor-1 (IGF-1) or vascular endothelial growth factor (VEGF)-165 in the cellular components of the ventricular system including the ependymal cell layer, choroid plexus [the primary cerebrospinal fluid (CSF)-producing cells of the central nervous system (CNS)] and spinal cord central canal leads to trophic factor delivery throughout the CNS, delayed motor decline and a significant extension of survival in SOD1(G93A) transgenic mice. Interestingly, when IGF-1- and VEGF-165-expressing AAV4 vectors were given in combination, no additional benefit in efficacy was observed suggesting that these trophic factors are acting on similar signaling pathways to modestly slow disease progression. Consistent with these findings, experiments conducted in a recently described in vitro cell culture model of ALS led to a similar result, with both IGF-1 and VEGF-165 providing significant motor neuron protection but in a nonadditive fashion. These findings support the continued investigation of trophic factor-based therapies that target the CNS as a potential treatment of ALS.


[Identification of knowledge deficits of pharmacy students at the beginning of the fifth year of pharmacy practice experience: Proposals to change the content of academic programs].
In France, community pharmacy students performed a hospital pharmacy practice experience during the 5th year of the university curriculum. The purpose of a part of the content of the academic teaching program delivered before this practice experience is to prepare the students for their future hospital activities. It should enable them for the practical use of knowledge in order to improve pharmacotherapy, laboratory diagnosis and monitoring of patients' care. The aim of this study was to show if there are gaps in this program. Fourteen students performing their clerkship in a teaching hospital were invited to highlight these gaps when they were gradually immersed in the pharmaceutical care. They did so under the careful observation of hospital pharmacist preceptors. These practitioners referred to professional guidelines, documentary tools used in daily clinical practice and publications supporting their pharmaceutical care practices. Shortcomings and gaps identified were: how to communicate with other healthcare professionals and the content of verbal exchanges, how to conduct a patient-centered consultation, documentation tools required for relevant pharmacist' interventions, codification of pharmacist's interventions, risks related to drug packaging and benefit risk assessment of health information technologies. These gaps represent a handicap by delaying the process that led to move from student to healthcare professional. Hospital pharmacist preceptors have to fill in these gaps before engaging students in pharmaceutical care. These results invite to revise partly the content of the academic teaching program delivered before the 5th year hospital pharmacy practice experience.


The possible fate of crystal harbouring larvae of Haemonchus contortus.
An examination of the occurrence of crystalline inclusions in the intestinal cells of fourth and fifth stage Haemonchus contortus revealed that a high percentage of inhibited early fourth stage larvae (L4) and developing L4 and a lower percentage of early fifth stage larvae (L5) harboured these crystals. Before the fourth moult crystals were falling into pieces, indicating that worms harbouring crystals can develop further. The presence of crystals may be associated with a retardation of development.


Analgesic effects of dextromethorphan and morphine in patients with chronic pain.
N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid analgesia in the animal model. The cough suppressant dextromethorphan is a clinically available NMDA-receptor antagonist. In this randomised, double-blind, placebo-controlled study 20 patients with chronic pain of several years duration were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100 mm) at the end of the morphine infusion were 38 (+/-6) for dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain intensity were comparable both at rest and at movement at all time points. The most common adverse effects reported were dizziness, nausea and sedation. There were no significant differences in either the incidence or severity of adverse effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief by intravenous morphine 15 mg in patients with chronic pain.


Reduction of postprandial blood glucose in healthy subjects by buns and flatbreads incorporated with fenugreek seed powder.
This study aimed to determine whether fenugreek seed powder could reduce the glycemic response and glycemic index (GI) when added to buns and flatbreads. In a randomised, controlled crossover trial, ten healthy human subjects (five men, five women) were given 50 g glucose (reference food, twice); buns (0 and 10 % fenugreek seed powder); and flatbreads (0 and 10 % fenugreek seed powder) on six different occasions. Finger prick capillary blood samples were collected at 0, 15, 30, 45, 60, 90 and 120 min after the start of the meal. The palatability of the test meals was scored using Likert scales. The incremental areas under the glucose curve value of buns and flatbreads with 10 % fenugreek (138 ± 17 mmol × min/L; 121 ± 16 mmol × min/L) were significantly lower than those of 0 % fenugreek bun and flatbreads (227 ± 15 mmol × min/L; 174 ± 14 mmol × min/L, P = <0.01). Adding 10 % fenugreek seed powder reduced the GI of buns from 82 ± 5 to 51 ± 7 (P < 0.01) and to the GI of flatbread from 63 ± 4 to 43 ± 5 (P < 0.01). These results suggest that replacing 10 % of refined wheat flour with fenugreek seed powder significantly reduces the glycemic response and the GI of buns and flatbreads. Thus, fenugreek powder may be a useful functional ingredient to reduce postprandial glycemia.


Balancing STING in antimicrobial defense and autoinflammation.
Rapid detection of microbes is crucial for eliciting an effective immune response. Innate immune receptors survey the intracellular and extracellular environment for signs of a microbial infection. When they detect a pathogen-associated molecular pattern (PAMP), such as viral DNA, they alarm the cell about the ongoing infection. The central signaling hub in sensing of viral DNA is the stimulator of interferon genes (STING). Upon activation, STING induces downstream signaling events that ultimately result in the production of type I interferons (IFN I), important cytokines in antimicrobial defense, in particular towards viruses. In this review, we describe the molecular features of STING, including its upstream sensors and ligands, its sequence and structural conservation, common polymorphisms, and its localization. We further highlight how STING activation requires a careful balance: its activity is essential for antiviral defense, but unwanted activation through mutations or accidental recognition of self-derived DNA causes autoinflammatory diseases. Several mechanisms, such as post-translational modifications, ensure this balance by fine-tuning STING activation. Finally, we discuss how viruses evade detection of their genomes by either exploiting cells that lack a functional DNA sensing pathway as a niche or by interfering with STING activation through viral evasion molecules. Insight into STING's exact mechanisms in health and disease will guide the development of novel clinical interventions for microbial infections, autoinflammatory diseases, and beyond.


Relating oxygen partial pressure, saturation and content: the haemoglobin-oxygen dissociation curve.
The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (S O2 ) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin-oxygen dissociation curve, a graphical representation of the relationship between oxygen satur-ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the S O2 in blood from patients with normal pH and S O2 >70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry (S pO2 ) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis (S aO2 ) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable S pO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined.


Treatment volume from total reference air kerma (TRAK) in intracavitory applications and its comparison with ICRU reference volume.
A systematic dosimetry study conforming to International Commission on Radiation Units and Measurements Report Number 38, was carried out for, cancer of Cervix Stage I and II cases at Tata Memorial Hospital. The reference Volume dimension were noted for each applicator. Also 3-D dosimetry was performed for selected cases, and actual geometric volume enclosed by various isodose surfaces were obtained. A relation was derived, which gave the volume enclosed by any isodose surface as a function of total reference air kerma of the sources in the applicator. The volume enclosed by reference isodose surface was compared with the product of its dimensions height, width, and thickness. The volume enclosed by any isodose surface of an intracavitary application can be easily derived from total reference air kerma of the sources within the applicator. Ratio of the volume enclosed by reference isodose surface with the product of its dimensions (HWT) could be a predictive parameter for clinical outcome, besides the reference volume specified by the report.


Long-term outcome of endoscopic ultrasound-guided pancreatic duct drainage using a fully covered self-expandable metal stent for pancreaticojejunal anastomosis stricture.
Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) has been proposed for pancreatic duct obstruction after failure of endoscopic retrograde pancreatography. We evaluate the long-term outcomes of EUS-PD using a fully covered self-expandable metal stent (FCSEMS) for pancreaticojejunal anastomosis (PJA) strictures following Whipple procedures. Twenty-three patients with PJA strictures underwent EUS-PD according to the findings of EUS-guided pancreatogram and the passage of the guidewire through PJA stricture (complete vs partial stricture) after failure of endoscopic retrograde pancreatography. Technical and clinical success, adverse events (AEs), and long-term outcomes were assessed. Technical and clinical success was achieved in all patients. The complete and partial strictures were 11 and 12, respectively. The direct transanastomotic and transmural plastic stenting in partial PJA stricture was successful in only three patients (13%). Therefore, 20 patients underwent EUS-guided transmural FCSEMS placement during the initial attempt. Early AEs, including abdominal pain (n = 3) and peripancreatic fluid collection (n = 1), occurred in four patients (17.4%). During the follow-up periods (median, 27.2 months; interquartile range [IQR], 18.7-40.6), five patients (21.7%) developed late AEs, including asymptomatic stent fracture at the gastric end (n = 3), asymptomatic stent migration (n = 1), and stent occlusion (n = 1). The total duration of stent placement was 27.2 months (IQR, 18.7-40.6), and the median number of stent revision was 2 (IQR, 1-2). In terms of safety and efficacy, EUS-PD with an FCSEMS showed favorable success and acceptable AEs rate and durable long-term outcomes.


Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation.
Serum polyamine oxidase (EC 188.8.131.52) is known to react in vitro with radio-labelled spermine4+ to produce di-oxidized spermine which must incorporate the label. Di-oxidized spermine was compatible with a radio-labelled compound2+ separated from the reaction mixture by ion-exchange chromatography. The compound was measured and had a half-life of about 2.3 h in tissue culture medium. It also rapidly and tightly bound to an unidentified serum component (gel-filtration chromatography indicated a complex of mol. wt 70,000) so that dissociation required treatment with strong acid (10N HCl). Findings suggest that the di-oxidized spermine, in either its free cationic or bound form, potently arrested cell proliferation. This arrest was non-cytotoxic and was confined to the G1 phase of the cell cycle. Products of di-oxidized spermine autodegradation, including trace amounts of stable and cytotoxic acrolein (arrested S phase), were unlikely to have contributed significantly to the arrest.


The development of anesthesia guidelines and standards.
Anesthesiology is considered a leading specialty with respect to medical risk management and patient safety. The American Society of Anesthesiologists (ASA) developed its first practice guidelines in 1968 and published its first set of stricter practice standards in 1986. The standards are detailed specifications for the minute-to-minute conduct of anesthesia practice. An impetus for ASA standards development has been the belief that physicians should develop their own standards rather than have them imposed by nonphysician third parties.


Non-vascularized partial joint transfer for Finger Proximal Interphalangeal joint reconstruction: a series of 9 patients.
Finger proximal interphalangeal joint (PIP) reconstruction after the destruction of parts of the joint remains challenging. Surgical techniques include implant arthroplasty, arthrodesis, free vascularized joint transfer, and non-vascularized bone and joint transfer. This study analyzes our experience after non-vascularized transfer in terms of range of motion, postoperative rehabilitation, and patient satisfaction. Between 2009 and 2014, ten patients underwent non-vascularized partial joint transfer for PIP joint reconstruction. One of them was lost to follow-up. Included patients had osteochondral partial joint transplants of 25-50% of the toes (n = 4) and the hand (n = 5). Range of motion (ROM), grip-, and pinch-strength were measured at the last follow-up control and compared to the healthy side. Patients were asked to score the pain at rest/ on load on a visual scale (VAS: 0 = no pain; 10 = excruciating pain). Satisfaction self-assessment was evaluated by asking the patients to grade their postoperative result as excellent, very good, good or poor. Mean follow-up period was 4.0 years (range 1.2-7.9 years). Mean PIP joint flexion was 93 ± 26° at the last follow-up control. Mean grip- and pinch-strength of the operated side at the last control were, respectively, 43 ± 18 kg and 8 ± 5 kg, close to the healthy side values (45 ± 15 kg and 9 ± 4 kg). Mean pain at rest/on load measured on a visual scale was, respectively, 0.3 ± 1 and 1.8 ± 2. Eight patients (89%) rated their operation as excellent, and one as poor. In this study, non-vascularized partial joint transfer provides a mobile and stable PIP joint 4 years after reconstruction. The surgical technique presented herein is complex depending on additional injuries but results in great patient satisfaction.


A simple and reliable continent bladder stoma constructed from bladder wall.
Patients presenting with recurrent bladder neck strictures or severe incontinence refractory to all forms of infravesical treatment usually require chronic catheterization or supravesical urinary diversion. As an alternative, we use a simple continent bladder stoma made from the bladder wall. After extraperitoneal bladder mobilization, a Lapides-like 4 x 8 cm U-shaped bladder flap is excised and sutured to a tube. Depending on the location of the stoma, the base of the flap can be chosen and/or the length of the flap can be adapted. After bladder neck closure the tube is reflected and, after incision and dissection of the detrusor in the middle of the base of the flap, embedded in Lich-Gregoir's technique. The distal end of the tube is then sutured to the stoma site. Five of our patients now have a minimum follow-up of 11 months (mean 17 months). All are continent with a bladder capacity between 250 and 560 ml. In two, stomal stenosis at the skin level required epifascial stomal revision.


Development of an intrinsic health risk prediction model for camera-based monitoring of older adults living alone.
The number of older adults in Korea is increasing, along with the number of depressed older patients. The causes of depression in older adults include social isolation with negligible interaction with others, irregular nutritional habits, and self-negligence, i.e., they do not engage in any activity. These factors, self-negligence, social isolation, and irregular nutritional habits, are defined as inherent health risks, and in this study, we detected them. These factors can only be derived through long-term monitoring, but the current monitoring system for older adults is severely limited as it focuses only on emergencies, such as "falls." Therefore, in this study, the goal was to perform long-term monitoring using a camera. In order to capture the physical characteristics of the older adults, the ETRI-Activity3D data were used for training, and the skeleton-based action recognition algorithm Posec3d was used. By defining 90 frames as the time taken for one action, we built a monitoring system to enable long-term monitoring of older adult by performing multiple action detection in one video. A reliable monitoring system, with 98% accuracy, 98% precision, 99% recall, and 98% F1, was successfully established for health monitoring of older adults. This older adult monitoring technology is expected to improve the quality of medical services in a medical environment as well as the objective, activities of daily living test, which does not depend on the observer through daily life detection.


Targeting Higher Intraoperative Blood Pressures Does Not Reduce Adverse Cardiovascular Events Following Noncardiac Surgery.
Intraoperative arterial hypotension is strongly associated with postoperative major adverse cardiovascular events (MACE); however, whether targeting higher intraoperative mean arterial blood pressures (MAPs) may prevent adverse events remains unclear. This study sought to determine whether targeting higher intraoperative MAP lowers the incidence of postoperative MACE. This single-center randomized controlled trial assigned adult patients at cardiovascular risk undergoing major noncardiac surgery to an intraoperative MAP target of ≥60 mm Hg (control) or ≥75 mm Hg (MAP ≥75). The primary outcome was acute myocardial injury on postoperative days 0-3 and/or 30-day MACE/acute kidney injury (AKI) (acute coronary syndrome, congestive heart failure, coronary revascularization, stroke, AKI, and all-cause mortality). The secondary outcome was 1-year MACE. In total, 458 patients were randomized (intention-to-treat population: 451). The cumulative intraoperative duration with MAP <65 mm Hg was significantly shorter in the MAP ≥75 group (median 9 minutes [interquartile range: 3 to 24 minutes] vs 23 minutes [interquartile range: 8-49 minutes]; P < 0.001). The primary outcome incidence was 48% for MAP ≥75 and 52% for control (risk difference -4.2%; 95% CI: -13% to +5%), the primary contributor being AKI (incidence 44%). Acute myocardial injury occurred in 15% (MAP ≥75) and 19% (control) of patients. The secondary outcome incidence was 17% for MAP ≥75 and 15% for control (risk difference +2.7; 95% CI: -4% to +9.5%). These findings do not support universally targeting higher intraoperative blood pressures to reduce postoperative complications. Despite a 60% reduction in hypotensive time with MAP <65 mm Hg, no significant reductions in acute myocardial injury or 30-day MACE/AKI could be found. (Biomarkers, Blood Pressure, BIS: Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery [BBB]; NCT02533128).


Response of liquid flow resistance to soil drying in seedlings of four deciduous angiosperms.
Soil-leaf resistance to liquid water flow (R) in moist and drying soil was compared in three-month-old seedlings of two drought tolerant (white [Quercus alba L.], post oak [Q. stellata Wangenh.]) and two drought sensitive forest species (sugar maple [Acer saccharum Marsh.], black walnut [Juglans nigra L.]). At high soil moisture (Ψs≥-0.3 MPa), R was higher in J. nigra than in the other species, and as soil water was depleted R increased most in this species. In contrast, the lowest resistance at all levels of soil moisture was observed in Q. stellata. At Ψs of -1.5 MPa, R of drought-sensitive J. nigra and A. saccharum was about twice as high as that of the two drought-tolerant Quercus species. The difference in R between the two Quercus species was much smaller than that between this pair and the other two species. These differences among species in flow resistance may be attributable to: 1) variation in the balance between root surface area and leaf area, 2) variation in the inherent absorption capacity of the root systems and in xylem water conducting systems or 3) differences in root permeability, shrinkage and mortality in severely stressed seedlings. As the soil dried, seedlings of all species exhibited pronounced reductions in transpiration rate, which prevented development of large water potential gradients between leaves and the soil. Reduction in transpiration in J. nigra was especially pronounced, resulting in a decrease in the soil-to-leaf water potential gradient in dry soil despite high flow resistance. The observed differences among species in flow resistance are correlated with natural distribution patterns.


Diazepam-induced NaCl solution intake: independence from renal factors.
Rehydrating rats injected with diazepam (8 mg/kg, SC) increased their intake of 2.0% NaCl solution. Neither bilateral nephrectomy nor bilateral ureter ligation interfered with the increased NaCl solution ingestion produced by diazepam. It is concluded that the increased intake of the NaCl solution is not secondary to renal water-electrolyte losses nor dependent upon intact renal benzodiazepine receptors.


Lesions of the rotator cuff footprint: diagnostic performance of MR arthrography compared with arthroscopy.
To evaluate the diagnostic performance of magnetic resonance arthrography (MR-A) of the shoulder in the diagnosis of rotator cuff tears involving the humeral insertion of the supraspinatus and infraspinatus tendon (footprint), using arthroscopy as the reference standard. The study population included 90 consecutive patients with history and clinical diagnosis of instability of the shoulder, rotator cuff tear or posterosuperior glenoid impingement. A total of 108 MR arthrograms were performed, since 18 patients had undergone a bilateral procedure. Arthroscopy, which was performed within 45 days after MR-A, was used as the reference standard. Sensitivity, specificity, accuracy, positive and negative predictive values were then calculated. Magnetic resonance arthrography showed a sensitivity of 92 % and a specificity of 78 % for the overall detection of tears involving the rotator cuff footprint. The diagnostic accuracy was 90 %, and the positive and negative predictive values were 95 and 64 %, respectively. Ten lesions were non-classifiable on surgery, of which eight were non-classifiable on MR-A also. Magnetic resonance arthrography is extremely accurate for the detection and classification of rotator cuff footprint tears. Most of these lesions are articular-sided (partial articular-sided supraspinatus tendon avulsion lesions) with predominance in younger patients and concealed type of tear (concealed interstitial delamination lesions).


The significance of a root-fungus association in two Carex species of high-alpine plant communities.
The relationship between roots of Carex firma, C. sempervirens and their commonly occuring dark septate fungal associates was examined. Two typical fungal associates were isolated and reinoculated onto aseptically grown seedlings of the two host species. Both isolates produced significant increases of dry matter production in C. firma compared with uninoculated controls. No growth stimulation was obtained in C. sempervirens. Shoot phosphorus concentrations were significantly increased in both host species by inoculation. The absence of growth stimulation in C. sempervirens may be due to carbon drain imposed by the fungus or to the fact that nutrients other than phosphorus are growth limiting. The nature and possible ecological significance of the root-fungus association is discussed and it is suggested that the relationship is mutualistic rather than parasitic.


The brassiere 'sign' - a distinctive marker in crush asphyxia.
The diagnosis of crush asphyxia typically relies on a history of chest or abdominal compression with the finding of skin petechiae and congestion. The following three cases of crush asphyxia demonstrate a distinctive pattern of petechiae and congestion associated with close-fitting clothing: Case 1, a 49-year-old woman who was crushed under a large hay bale; Case 2, a 35-year-old woman who was crushed between a wall and a car; Case 3, a 49-year-old woman who was crushed between a crane and the side of a truck. At autopsy in all three cases there were facial, conjunctival, neck and upper anterior chest petechiae. However, few or no petechiae, and reduced congestion, were observed in areas beneath the victims' brassieres. Deaths in these cases were all due to crush asphyxia, with the pattern of petechiae on the chests of the victims influenced by close-fitting clothing that had compressed cutaneous vasculature. This brassiere 'sign' provided a readily observable and easily recordable sign of crush asphyxia due to chest compression, and illustrated that vascular engorgement is necessary for the development of petechiae in these circumstances.


Chemical coagulation of combined sewer overflow: heavy metal removal and treatment optimization.
The coagulation of combined sewer overflow (CSO) was investigated by jar-testing with two commercial coagulants, a ferric chloride solution (CLARFER) and a polyaluminium chloride (WAC HB). CSO samples were collected as a function of time during various wet-weather events from the inlet of Boudonville retention basin, Nancy, France. Jar-tests showed that an efficient turbidity removal can be achieved with both coagulants, though lower optimum dosages and higher re-stabilization concentrations were obtained with the aluminum-based coagulant. Optimum turbidity removal also yielded effective heavy metal elimination. However, the evolution with coagulant dosage of Cu, Zn, Pb, Cr, soluble and suspended solids contents followed various patterns. The removal behaviors can be explained by a selective aggregation of heavy metal carriers present in CSO and a specific interaction between hydrolyzed coagulant species and soluble metals. Stoichiometric relationships were established between optimal coagulant concentration, range of optimal dosing, and CSO conductivity, thus providing useful guidelines to adjust the coagulant demand during the course of CSO events.


DNA sequences coding for the F18 fimbriae and AIDA adhesin are localised on the same plasmid in Escherichia coli isolates from piglets.
The adhesin-involved-in-diffuse-adherence (AIDA) afimbrial adhesin is produced by human, but not by animal, Escherichia coli, with the exception of German porcine verotoxigenic Escherichia coli (VTEC) [Clin. Diagn. Lab. Immunol. 8 (2001) 143]. Presence and localisation of DNA sequences (aidA) coding for and production of an AIDA adhesin were investigated in a collection of Belgian VTEC and non-VTEC E. coli isolated from piglets at weaning time. The 174 isolates were also studied by colony hybridisation for the presence of DNA sequences coding for the Stx2e verocytotoxin and the F18 fimbrial adhesin (fed): 71 were Stx2+F18+AIDA+, 26 were F18+AIDA+, 12 were AIDA+, two were Stx2+AIDA+, and one was Stx2+ only. Fifty-four of the 58 (F18+)AIDA+ isolates tested positive in a western blotting assay with an immune serum raised against the AIDA protein. Hybridisation with the AIDA gene probe on plasmid DNA profiles identified a probe-positive plasmid band in the 10 AIDA+ and in 24 of the 25 F18+AIDA+ isolates studied. Moreover in F18+AIDA+ isolates, only one plasmid band hybridised with both F18 and AIDA probes. These results confirm the presence of aidA-related genes in not only VTEC, but also non-VTEC, isolates from piglets and the production of an antigenically AIDA-related protein by the majority of probe-positive E. coli. Moreover the plasmid DNA hybridisation results suggest a localisation on the same plasmid of the aidA- and fed-related DNA sequences.


Phase II trial of carboplatin in combination with etoposide in locally advanced large cell carcinoma and adenocarcinoma of the lung.
A total of 18 patients with locally advanced (Stage III) adenocarcinoma and large cell undifferentiated carcinoma of the lung, previously untreated, were enrolled in a Phase II trial. Treatment consisted of carboplatin 325 mg/m2, day 1 and etoposide 100 mg/m2 on days 2 and 3. All patients were evaluable for response. Of these, one patient had a partial response (5.5%; confidence interval 0-24%). Toxicity comprised mainly leukopenia and anaemia. Other toxicities were mild. This Phase II study evidenced a poor response rate for these regimes on adenocarcinoma and large cell undifferentiated carcinoma of the lung.


Unique and overlapping substrate specificities of caspase-8 and caspase-10.
Although caspase-8 has an established role as an initiator of death receptor-mediated apoptosis, the function of its closest homolog, caspase-10, is almost completely unknown. To gain a closer insight into the physiological function of caspase-10, we compared the cleavage of known caspase-8 substrates by both initiator caspases. We demonstrate that caspase-10 and -8 have overlapping cleavage preferences for several substrates such as the kinases RIP and PAK2. Interestingly, in other substrates, such as the Bcl-2 protein Bid, we found additional and distinct cleavage sites for both caspases, which might have important consequences for mitochondrial targeting and propagation of the death signal. Caspase-8 and -10 also caused different interchain cleavage patterns of their enzyme precursors. Together, these results suggest that caspase-8 and -10, despite having overlapping functions, also have selective substrate cleavage specificities and might thereby exert nonredundant roles in apoptosis signaling.


Valvular lesions in patients with systemic lupus erythematosus and antiphospholipid syndrome: an old disease but a persistent challenge.
Valvular heart disease is common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Immunologic insult plays a fundamental role in its pathogenesis but data on the role of antiphospholipid antibodies have been inconsistent, particularly regarding SLE-associated valvular lesions. Although timely diagnosis is essential to prevent progression of valvular lesions, treatment remains a challenge because of the lack of large systematic studies. This article reviews and summarizes recent information relating to valvular damage in these two autoimmune diseases, and highlights some important questions that need to be answered.


Sequential heavy metals extraction from polluted solids: influence of sulfate overconcentration.
The effect of sulfate on the chemical partitioning of Cu, Cd, and Pb in solid phases was assessed in this study. Modified BCR sequential extraction, speeded up by focused ultrasound, was systematically applied to various mixtures of typical geochemical solid phases (an artificial goethite spiked with Cu, Cd, and Pb and natural clays), with or without the addition of calcium sulfate. Sulfate was added so that three different concentrations were found in sequential extracts: 0.5, 1, and 1.5 g/L of sulfate. First, the results suggested that the goethite-surface adsorption sites for sulfate are limited. Then, significant changes in Cd and Pb fractionation were observed in the presence of sulfate, whereas Cu remained strongly adsorbed on the solid phases. The main modifications observed in all the studied samples were a decrease in metal amounts in the first three fractions to the profit of an increase in the residual fraction. These results suggested that the adsorption of metals onto the studied solids was enhanced by the presence of sulfate. From these considerations, some hypotheses are advanced to describe the behavior of Cu, Cd, and Pb and their adsorption mechanisms on solid phases in sulfate-rich systems.


Design and synthesis of a tetrahydropyran-based inhibitor of mammalian ribonucleotide reductase.
A tetrahydropyran-based inhibitor (2) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized based on the heptapeptide, N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed that 2 is indeed a competent inhibitor, albeit less potent than 1.


Parahiraciini planthoppers with elongate head from Vietnam: a new genus and species Pumatiraciavenosa gen. et sp. nov. and first record of Laohiraciaacuta Constant, 2021 (Hemiptera, Fulgoromorpha, Issidae).
The new genus Pumatiraciagen. nov. is described to accommodate a new species, P.venosagen. et sp. nov. from Pu Mat National Park in Vietnam. The new genus is placed in the subtribe Parahiraciina of the Parahiraciini. It is compared with the genera Laohiracia Constant, 2021, Macrodarumoides Che, Zhang et Wang, 2012, Pseudochoutagus Che, Zhang et Wang, 2011, and Rostrolatum Che, Zhang et Wang, 2020 with which it shares possessing an elongate head. Illustrations of habitus, details, and male genitalia are given as well as a distribution map and photographs of the habitat. Laohiraciaacuta Constant, 2021 is recorded for the first time from Vietnam, Pu Luong National Park; living specimens and habitat are illustrated, and the distribution map updated. The Parahiraciini fauna of Vietnam now comprises 14 species belonging to 11 genera.


The cytotoxic evaluation of mineral trioxide aggregate and bioaggregate in the subcutaneous connective tissue of rats.
The purpose of this study was to evaluate and compare the cytotoxic effects of ProRoot MTA and DiaRoot BA, a bioceramic nanoparticulate cement, on subcutaneous rat tissue. Fifty Sprouge Dawley rats were used in this study. Polyethylene tubes filled with ProRoot MTA and DiaRoot BioAggregate, along with a control group of empty, were implanted into dorsal connective tissue of rats for 7, 15, 30, 60, and 90 days. After estimated time intervals the rats were sacrificed. The specimens were fixed, stained with hematoxylin and eosin, and then evaluated under a light microscope for inflammatory reactions and mineralization. All groups evoked a severe to moderate chronic inflammatory reaction at 7 and 15 days, which decreased with time. Both the MTA and BioAggregate groups showed similar inflammatory reactions, except at 90 days when MTA showed statistically significant greater inflammation (p>0.05). The MTA group showed foreign body reaction at all times. Compared to BioAggregate, MTA showed significantly more foreign body reaction at 60 and 90 days (p<0.0001). After 30 days foreign body reaction of BioAggregate decreased significantly. Both MTA and BioAggregate groups showed similar necrosis at 7 and 15 days (p=0.094 and p=0.186 respectively). No necrosis was observed after 15 days. Similarly there was no fibrosis after 30 days for both MTA and BioAggregate groups (p>0.05). Since DiaRoot BioAggregate showed significantly better results than MTA, we can conclude that it is more biocompatible. However, further studies are required to confirm this result.


Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones.
Novel 1-(1-benzoylindoline-5-sulfonyl)-4-phenyl-4,5-dihydroimidazolon es 3 synthesized show highly potent and broad cytotoxicities. Among them compound 3b (DW2143) exhibits much more potent cytotoxicities than doxorubicin and highly effective antitumor activities against murine (3LL, Colon 26) and human xenograft (NCI-H23, SW620) tumor models.


Present and Future Therapies for Chronic Hepatitis B.
Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.


Thoracic splenosis: History is the key.
Splenosis is an acquired ectopic autotransplantation of splenic tissue; that occurs after traumatic splenic rupture and splenectomy [1]. Splenosis is a rare but benign disease, and the diagnosis can be challenging as the multiple incidentally found nodules could mimic malignancy [2]. Abdominopelvic Splenosis is thought to occur in as many as 65% of cases of splenic rupture [1]. However, Thoracic Splenosis is rare and usually involve the left parietal and visceral pleura [1,2]. Intraparenchymal lesions are less common but have been reported in cases of parenchymal and diaphragm laceration [1,2]. Taking a thorough history is of utmost importance, as these patients usually present more than two decades after the splenic traumatic rupture. The use of commonly available nuclear studies will further confirm the diagnosis [3]. This will help to avoid unnecessary procedures, like biopsies; and prevent the potential complications. We present a case of Thoracic Splenosis that highlights the importance of taking a detailed history; and the importance of using nuclear studies for the diagnosis. Further adding to its uniqueness, this case showed with multiple intraparenchymal nodules which is a less common presentation of Splenosis.


Activity of the new OSBP inhibitor Y18501 against Pseudoperonospora cubensis and its application for the control of cucumber downy mildew.
Y18501 is a new oxysterol-binding protein inhibitor (OSBPI) with a similar structure to oxathiapiprolin. Y18501 showed strong inhibitory activities against Phytophthora spp. and Pseudoperonospora cubensis, with EC50 ranging from 0.0005 to 0.0046 μg/mL. It also had good control efficacy on cucumber downy mildew (CDM) in the green house and in the field, and could effectively inhibit different development stages of P. cubensis, especially for sporangiophore production, sporangial production, mycelium extension, and elongation of germ tube. In addition, Y18501 showed excellent protective and curative activities against P. cubensis. It also had acropetal systemic mobility in the cucumber leaves, and could be taken up and translocated to the upper leaves more effectively from the lower leaves than from the roots. Y18501 had poorer permeability in cucumber leaves compared to oxathiapiprolin. The simultaneous application of Y18501 and chlorothalonil could significantly promote the inhibition of P. cubensis.


Influence of Crestal Implant Position and a Smooth Collar on Marginal Bone Level: A 2-Year Retrospective Radiographic Analysis.
This retrospective study evaluated the survival rate and the clinical outcome of an endosseous implant system, as well as the marginal bone level (MBL) and the impact of the machined collar neck position on crestal bone level changes up to 2 years later. A total of 96 implants were placed in 57 patients and loaded with a final restoration after at least 3 months of healing: 15 implants were immediately placed into fresh extraction sockets, and 81 were placed in healed ridges. Marginal bone loss around implants was determined radiographically at 12 to 24 months postloading. The effects on marginal bone loss of the site (mandible vs maxilla), location (anterior vs posterior), immediate vs delayed implant, smoking habit, sex, implant length and diameter, prosthesis type (screw-retained/cemented), and the machined collar position were evaluated. The implant survival rate was 98.96% at 1 year. The mean MBL decreased significantly (0.238 mm) between baseline and loading (P < .001; post hoc test) and decreased by 0.154 mm between loading and 1 year, but this was not significant (P = .085; post hoc tests). After 2 years, the mean MBL decreased significantly (0.263 mm) between baseline and loading (P < .001) and decreased by 0.111 mm between loading and 1 year and by 0.199 mm between loading and 2 years, but these were not significant (P > .05; post hoc tests). The mean bone loss after 1 and 2 years was not significantly associated with implant type or site, smoking habit, or type of implant surgery (P = .792). However, the mean bone loss was significantly associated with the type of prosthesis and was significantly greater for cemented prostheses compared to screw-retained prostheses. A supracrestal position of the machined collar (tissue level) was associated with no bone loss, while placing the collar below the alveolar crest led to bone loss over 2 years. Of the factors evaluated, marginal bone loss after 1 and 2 years was significantly associated with prosthesis type and the machined collar position.


Epidemiology of Mycobacterium bovis and Mycobacterium tuberculosis in animals: Transmission dynamics and control challenges of zoonotic TB in Ethiopia.
Mycobacterium tuberculosis complex is the cause of tuberculosis (TB) in humans and other animals. Specifically, Mycobacterium bovis (M. bovis) and Mycobacterium tuberculosis (M. tuberculosis) are highly pathogenic mycobacteria that may infect different animal species and are the sources of TB in humans. The objective of this paper was to review the epidemiology of M. bovis and M. tuberculosis in animals. The review also highlighted the transmission dynamics of M. bovis and M. tuberculosis in humans and animals and control challenges of zoonotic TB in Ethiopia. The literature review focused on scientific peer-reviewed articles from studies exclusively conducted in Ethiopia that were published from 1998 to 2017. Husbandry system, breed and herd size have significant role in the epidemiology of bovine tuberculosis (BTB) in Ethiopia. The information presented reveals that different strains of M. bovis are widely distributed in domestic animals predominantly in the Ethiopian cattle and the main strain was found to be SB1176. In addition, the isolation of M. tuberculosis from domestic animals in different settings signifies the circulation of the agent between humans and animals in Ethiopia. The life styles of the Ethiopian communities, close contact with domestic animals and/or the habit of consuming raw animal products, are suggested as the main factors for transmission of M. bovis and M. tuberculosis between human and animal which may have impact on the TB control program in human. In Ethiopia, a human TB control program has been widely implemented, however, the role of animal in the transmission of the causative agent has been neglected which could be one of the challenges for an effective control program. This warrants the need for incorporating animal TB control programs using "One Health" approach for effective TB control for both human and animal.


Intraductal tubulopapillary neoplasm of the bile duct: A case report and review of the published work.
Recent studies have suggested that a peculiar tumor mimicking intraductal tubulopapillary neoplasms (ITPN) of the pancreas can develop in the bile duct. Here, we present a similar case and review the published work on the newly proposed biliary neoplasm. A 68-year-old woman was referred to us for further evaluation of a liver mass. On imaging, the tumor was 40 mm in size and intraductal in location, and was enhanced slightly on the contrast-enhanced computed tomography. No mucin overproduction was found. She underwent right hepatectomy for suspected intraductal papillary neoplasm of the bile duct. The tumor histologically consisted of the biliary-type epithelium arranged in a tubular architecture within the dilated bile duct. Tumor cells had features of high-grade dysplasia but no stroma invasion. No expressions of MUC2 and MUC5AC were noted. On molecular studies, KRAS and GNAS appeared to be wild-type genotypes. These features were in keeping with ITPN. In the published work review, "biliary ITPN" described in four manuscripts were characterized by predominantly intrahepatic/hilar in location, histological tubular architecture, negative expressions of MUC2 and MUC5AC, and uncommon alterations of KRAS, GNAS and BRAF. Although invasive malignancy was present in 71%, the outcome was favorable with the 5-year survival expected to be approximately 90%. Biliary ITPN are supposedly uncommon, but a greater awareness of this condition may give more chance to diagnose the underrecognized neoplasm.


Peptidomics as a useful tool in the follow-up of food bioactive peptides.
There is an intense research activity on bioactive peptides derived from food proteins in view of their health benefits for consumers. However, their identification is quite challenging as a consequence of their small size and low abundance in complex matrices such as foods or hydrolyzates. Recent advances in peptidomics and bioinformatics are getting improved sensitivity and accuracy and therefore such tools are contributing to the development of sophisticated methodologies for the identification and quantification of peptides. These developments are very useful for the follow-up of peptides released through proteolysis either in the food itself through the action of endogenous peptidases during processing stages like fermentation, drying or ripening, or from food proteins hydrolyzed by commercial peptidases or microorganisms with proteolytic activity. This chapter is presenting the latest advances in peptidomics and its use for the identification and quantification of peptides, and as a useful tool for controlling the proteolysis phenomena in foods and protein hydrolyzates.


Neoadjuvant therapy for muscle-invasive bladder cancer: Current clinical scenario, future perspectives, and unsolved questions.
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for patients with muscle-invasive bladder cancer (MIBC). However, the implementation of NAC is lower than desirable mainly due to its limited impact on overall survival, patients' comorbidities and the lack of predictive biomarkers to select those patients most likely to benefit from NAC. In the last decade, improved molecular MIBC characterisation, the identification of potential predictive and prognostic biomarkers as well as the incorporation of new effective therapies with a better toxicity profile, such as immunotherapy, has changed the treatment paradigm for MIBC. Therefore, the main goal for the near future is to introduce these clinical and translational advances into routine clinical practice to personalise treatment for each patient and increase the opportunity to implement bladder preservation strategies. The present review focuses on the current status of NAC in MIBC, unsolved questions and future therapeutic approaches.


Intratracheal cell transfer demonstrates the profibrotic potential of resident fibroblasts in pulmonary fibrosis.
Pulmonary fibrosis is a devastating disease for which there are few effective therapies. Activated fibroblasts form subepithelial clusters known as fibroblastic foci, which are characterized by excessive collagen deposition. The origin of activated fibroblasts is controversial and needs to be clarified to understand their pathogenicity. Here, using an intratracheal adoptive cell transfer method, we show that resident fibroblasts in alveolar walls have the highest profibrotic potential. By using collagen I(α)2-green fluorescent protein and neural/glial antigen 2-DsRed fluorescent reporter mice, we identified resident fibroblasts and pericytes in the alveolar walls based on surface marker expression and ultrastructural characteristics. In the early phase of bleomycin-induced pulmonary fibrosis, activated fibroblasts migrated into epithelium-denuded alveolar airspaces. Purified resident fibroblasts delivered into injured alveoli by an intratracheal route showed similar activated signatures as activated fibroblasts and formed fibroblastic foci. Neither pericytes nor epithelial cells had the same profibrotic potential. Transferred resident fibroblasts highly up-regulated profibrotic genes including α-smooth muscle actin and were a significant source of collagen deposition. These data provide insights into the cellular mechanisms of fibrogenesis and show intratracheal cell transfer to be a useful tool for exploring novel therapeutic targets against pulmonary fibrosis.


Schwannoma (neurilemmoma) of tongue: A rare case presentation and review of literature.
It seems that schwannomas of the tongue base originate from branches of the glossopharyngeal, vagus, or hypoglossal nerves. Additionally, complete trans-oral surgical excision is an efficient method to remove them.


Efficient synthesis of tetradecafluoro-4-phenylheptan-4-ol by a Cannizzaro-type reaction and application of the alcohol as a bulky Martin ligand variant for a new anti-apicophilic phosphorane.
Alcohols 8 bearing two identical perfluoroalkyl groups were prepared by the reaction of the corresponding perfluoroalkyl phenyl ketones 7 with 0.5 equivalents of t-BuOK via Cannizzaro-type disproportionation. Utilizing the new bulky bidentate ligand with two n-C(3)F(7) groups generated from 8c, anti-apicophilic phosphorane 5a and its stable isomer 6a were synthesized. The crystal structures of 5a and 6a were slightly affected by the steric repulsion of heptafluoropropyl groups. Kinetic studies on the isomerization of 5a to 6a showed that the new ligand was effective for decreasing the isomerization rate compared with its C(2)F(5) analog 3a to about half.


Emotional functioning in anorexia nervosa patients: adolescents compared to adults.
Studies concerning eating disorder patients have revealed the presence of alexithymia, depressive, and anxiety disorders. We compared these aspects of emotional functioning in two groups of anorexia nervosa (AN) patients: adolescents vs. adults. Forty-eight adolescent anorexia nervosa patients (ADO) and 23 adult anorexia nervosa patients (ADU) completed a battery of tasks and questionnaires to measure these different aspects of emotional functioning and to control for differences of a more general cognitive nature. Both groups showed marked resemblance; both had high alexithymia scores and performed worse on emotional tasks measuring aspects of alexithymia. Furthermore, both groups showed high percentages of depressive and anxiety disorders, with the ADU group scoring only higher on specific and social phobia than the ADO group. Adult and adolescent AN patient groups do not differ substantially with respect to emotional functioning.


Intraocular lens power calculation after decentered photorefractive keratectomy.
A 59-year-old patient who had photorefractive keratectomy (PRK) to correct high unilateral myopia developed a progressive nuclear cataract. Phacoemulsification and intraocular lens (IOL) implantation were performed. However, determination of IOL power using automated keratometry and computerized videokeratography was not successful in this case of high axial myopia because of a decentered ablation zone, resulting in too-steep keratometric readings. Postoperative hyperopia could only be corrected by an IOL exchange. Because it may not be possible to determine the exact keratometric values for IOL calculation after PRK, subtracting the change in refraction induced by PRK from the preoperative keratometric readings might have been more accurate in this patient.


Status of Tenure Among Black and Latino Faculty in Academic Medicine.
Tenure has been used for years to recruit, promote, and retain faculty in higher education and has been associated with job security and academic freedom. Absence of tenure and not being in tenure-earning tracks is grouped with the challenges faced by underrepresented minorities in academic medicine. Those challenges include being found at the assistant professor rank more often, having more clinical responsibilities, and not being in leadership positions as often as compared to non-minority faculty. The role of tenure and tenure tracks is unclear as it relates to the presence of minority faculty. This article presents a look at the status of tenure among black and Latino faculty in academic medicine at US medical schools.


Cost-effectiveness of empagliflozin in the UK in an EMPA-REG OUTCOME subgroup with type 2 diabetes and heart failure.
Heart failure (HF) and type 2 diabetes (T2D), common co-morbidities, translate into worse patient prognoses and higher direct costs than for either condition alone. Empagliflozin has been shown to markedly reduce cardiovascular (CV) deaths and HF hospitalizations (HHF) in HF patients with T2D. This study evaluated the lifetime cost-effectiveness of supplementing standard of care (SoC) with empagliflozin, relative to SoC alone, in HF patients with T2D from the UK payer perspective. An existing discrete-event simulation model was adapted for the economic evaluation. Risk equations developed from time-dependent parametric survival analyses using patient-level HF subpopulation data from the EMPA-REG OUTCOME trial were employed to predict CV and renal events. Non-CV death, utility weights, and costs were drawn from UK sources. Quality-adjusted life years (QALYs) and costs were discounted at 3.5% per annum. Relative to SoC, empagliflozin with SoC yielded fewer first HHF, recurrent HHF, CV death, and non-fatal myocardial infarction but more non-fatal stroke events. Empagliflozin with SoC vs. SoC alone was associated with increased average life expectancy (10.80 vs. 9.59 LYs) and quality of life (6.27 vs. 5.62 QALYs), though at higher lifetime cost (£18 197 vs. £16 829) per person, resulting in an incremental cost-effectiveness ratio of £2093 per QALY. The probability of empagliflozin being cost-effective in the HF subpopulation at a £20 000 per QALY willingness-to-pay threshold was 91%. This analysis suggests that adding empagliflozin to SoC in HF patients with T2D constitutes a cost-effective use of UK healthcare resources and may provide long-term health benefits to patients.


fac-Tricarbonyl[hydroxybis(2-pyridyl)methanolato-kappa3N,O,N']rhenium(I).
The Re(I) centre in the title compound, [Re(C(11)H(9)N(2)O(2))(CO)(3)] or fac-Re(CO)(3)(dpkO,OH) [dpkO,OH is hydroxybis(2-pyridyl)methanolato], (I), is in a pseudo-octahedral environment in which the major distortion is due to the constraints associated with the tridentate binding of the dpkO,OH anion. The carbonyl groups are orthogonal, with an average C-Re-C angle of 90.2(3) degree. The molecules pack in stacks of antiparallel tapes of (I) interlocked via a network of hydrogen bonds.


Sensitivity of in vitro digestible energy determined with computer-controlled simulated digestion system and its accuracy to predict dietary metabolizable energy for roosters.
Two experiments were conducted to validate the sensitivity and accuracy of in vitro digestible energy (IVDE) determined with a computer-controlled simulated digestion system (CCSDS) to predict metabolizable energy (ME) of diets for roosters. In experiment 1, soybean hulls were added to a basal diet (calibration diet 1) at 2.06, 4.12, 6.17, 8.23, 10.28, 12.32, or 14.37% of the diets (calibration diets 2-8) to produce an interval of approximately 80 kcal ME/kg. The sensitivity was measured by comparing the determined and actual IVDE of the diets. With these data, a linear model was developed to predict ME from IVDE. In experiment 2, validation diets were identical except they were composed of different cereal ingredients. For each diet, the correlations and ratios between IVDE and ME were analyzed to test the sensitivity of IVDE to predict ME across different ingredients. In experiment 1, a slope of 0.9899 was calculated in a linear regression of determined IVDE on actual IVDE (R2 = 0.9998; P < 0.01). The ratio of determined IVDE to actual IVDE was 0.9878. The ratio of IVDE to apparent metabolizable energy (AME) and to nitrogen-corrected AME (AMEn) was 1.03 and 1.05, respectively. The linear models to predict ME from IVDE were AME = 0.8449 × IVDE + 451 (R2 = 0.9812, residual standard deviation [RSD] = 28 kcal/kg; P < 0.01) and AMEn = 0.8357 × IVDE + 436 (R2 = 0.9821, RSD = 27 kcal/kg; P < 0.01). In experiment 2, a significant simple correlation was observed between the IVDE and AME or AMEn of validation diets (r > 0.97; P < 0.01). The ratio of IVDE to AME and to AMEn was 1.04 and 1.05, respectively. Predicted and determined AME or AMEn of 8 validation diets differed by less than 100 kcal/kg. The regression of determined AME or AMEn against predicted AME or AMEn (R2 ≥ 0.9466; P < 0.01) resulted in an overlapped line where Y = X. These results suggest the IVDE determined with CCSDS is highly sensitive and can be used to accurately predict the ME of diets for roosters across a wide range of cereal grains.


Spontaneous disappearance and recurrence of impending macular hole: a case report.
There have been several reports of spontaneous closure and reopening of a macular hole, however, in most of those cases, it was observed in eyes post vitrectomy. Here, we report a case of multiple episodes of spontaneous disappearance and recurrence of impending macular hole (stage 1B macular hole) with no history of previous surgery. A 76-year-old Japanese man presented with a primary complaint of reduced visual acuity in his right eye. On initial examination, the visual acuity in his right and left eye was 0.4 and 0.01, respectively. He had previously been diagnosed as having macular degeneration of unknown origin in his left eye. Optical coherence tomography imaging confirmed vitreomacular traction and impending macular hole in his right eye. After a 1-week follow-up period, posterior vitreous detachment was detected, and the impending macular hole appeared to be resolved. Two months later, the impending macular hole had completely disappeared and his visual acuity had improved to 0.9. Six months later, he again noticed decreased vision in his right eye. An examination revealed that his visual acuity had dropped to 0.4, and there was a recurrence of impending macular hole. An optical coherence tomography examination showed no definitive findings of vitreous traction, and, 1 month later, spontaneous disappearance was observed again and his visual acuity improved to 0.7. In this case, both the initial onset and the recurrence involved impending macular hole, however, the optical coherence tomography findings differed at each examination. These findings suggest that some causes other than vitreous traction were responsible for both the spontaneous disappearance and recurrence of the impending macular hole in this present case.


Pyocystis.
A case of pyocystis occurring in a woman after supravesical urinary diversion for complicated neuropathic bladder is reported. Treatment consisted of a vaginal vesicostomy. Indications for the precedure and the problems associated with it are discussed with special emphasis on sexual intercourse.


Electric and Magnetic Hotspots via Hollow InSb Microspheres for Enhanced Terahertz Spectroscopy.
We study electric and magnetic hotspots in the gap between hollow InSb microspheres forming dimers and trimers. The outer radius, core volume fraction, distance, and temperature of the microspheres can be chosen to achieve field enhancement at a certain frequency corresponding to the transition between energy levels of a molecule placed in the gap. For example, utilizing 80 μm radius spheres at a gap of 2 μm held at a temperature of 295 K, allow electric field intensity enhancements of 10-2880 and magnetic field intensity enhancements of 3-61 in the frequency window 0.35-1.50 THz. The core volume fraction and the ambient temperature affect the enhancements, particularly in the frequency window 1.5-2 THz. Electric and magnetic hotspots are promising for THz absorption and circular dichroism spectroscopy.


Evaluation of a new ultrashort triple therapy for Helicobacter pylori disease.
1-week proton pump inhibitor-based triple therapies are considered the most effective and convenient drug combinations for curing Helicobacter pylori infection. Short therapies, lasting less than 1 week have been investigated rarely. To assess the efficacy and tolerability of a 3-day lansoprazole triple therapy after 1 day of lansoprazole pre-treatment. Seventy H. pylori-positive (rapid urease test and histology) patients received LAzT3 regimen (lanzoprazole 30 mg b.d. and azithromycin 500 mg o.m. for 3 days; tinidazole 2000 mg o.m. on day 1 and 1000 mg o.m. on days 2-3) after 1 day of lansoprazole pretreatment. Patients with active ulcer received lansoprazole 30 mg o.m. for an additional 4 weeks. Follow-up gastroscopy was carried out 4-6 weeks after completion of therapy. Eradication was defined as negative histology and rapid urease test. Four patients failed to attend the follow-up endoscopy. One patient complained of minor side-effects. H. pylori was eradicated in 57 of 66 patients suitable for evaluation, with a per-protocol cure rate of 86.3% (95%CI: 76-94%), and an intention-to-treat cure rate of 81.4% (95%CI: 70-90%). This new ultrashort triple therapy including lansoprazole, azithromycin and tinidazole seems to be effective in eradicating H. pylori. It is safe and well-tolerated, and may be taken into consideration as a valid alternative to the better known and widely used 1-week proton pump inhibitor-based triple therapies.


[Association between urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery].
To test the hypothesis that Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for acute kidney injury (AKI) in patients after cardiac surgery. 33 cases undergoing cardiac surgery were divided into AKI group and Non-AKI group according to the AKI criteria. The concentration of urine NGAL at different time points were measured. (1) Nine of 33 cases (27%) developed postoperative AKI, but diagnosis with serum creatinine was only 12-48 hours after cardiac surgery. (2)Urinary concentrations of NGAL at 2 h after cardiac surgery in patients who did not developed AKI were significantly higher compared with those of preoperative (P < 0.001). Urinary concentrations of NGAL at 2 h and 4 h after cardiac surgery in patients who developed AKI were significantly higher compared with those of preoperative (P < 0.001). (3) The mean urinary NGAL concentrations in patients who developed AKI were significantly higher after surgery compared with patients who did not develop AKI (P < 0.01). (4) Urinary concentrations of NGAL/Ucr at 2 h and 4 h after cardiac surgery in patients who did not developed AKI were significantly higher compared with those of preoperative (P < 0.05). Urinary concentrations of NGAL/Ucr at 2 h and 4 h after cardiac surgery in patients who developed AKI were significantly higher compared with those of preoperative (P < 0.01). (The mean urinary concentrations of NGAL/Ucr in patients who developed AKI were significantly higher after surgery compared with patients who did not develop AKI (P < 0.01). (6) For concentrations in urine of NGAL at 2 h after surgery, sensitivity was 0.7125, and specificity was 0.7307 for a cutoff value of 250 microg/L. For concentrations in urine of NGAL/Ucr at 2 h after surgery, sensitivity was 0.8127, and specificity was 0.7839 for a cutoff value of 250 microg/mmol. (7) Urinary concentrations of NGAL at 2 h after cardiac surgery was significantly associated with serum creatinine 12 h postoperative (R = 0.638, P < 0.05). The incidence of AKI in patients after cardiac surgery is high, which accounted for 27%. The amount of NGAL and NGAL/Ucr in urine at 2 h after cardiac surgery were the powerful independent predictor of acute renal injury and urine concentrations of NGAL/Ucr is more sensitive.


Cytokeratin provides a specific marker for human arachnoid cells grown in vitro.
Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form nonoverlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis.


Gastrin: growth enhancing effects on human gastric and colonic tumour cells.
Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (10 micrograms mouse-1 day-1, subcutaneous injection). MKN45 xenografts showed a greater response to continuously administered gastrin (osmotic mini-pumps, (10 micrograms mouse-1 day-1) when compared to the same dose given via a subcutaneous bolus injection. The hormone-treated xenografts had a two-fold increase in tumour cross-sectional area and growth rate when compared to saline-treated controls. Dose-response studies revealed that 0.4 micrograms gastrin mouse-1 day-1 appeared to be the minimally effective dose. As gastric and colorectal tumour cells show a trophic response to gastrin, antagonists of the gastrin receptor may prevent this effect causing tumour stasis. The gastric tumour cell line, MKN45, is gastrin-responsive and would be an ideal model for screening potent receptor antagonists.


In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres.
Treatment of many intracellular infections in the mononuclear phagocytic system (MPS), requires targeting of antibiotics by a drug delivery system. The objective of this study was to examine whether the particular nature of microspheres, made of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the activation of monocyte-macrophages. Placebo and gentamicin sulfate containing microspheres were incubated with J774 murine monocyte-macrophages and fresh human blood monocytes. Phagocytosis became more efficient with increasing polymer hydrophobicity, whereas opsonization of the particles in serum exerted inconsistent effects. Monocyte activation was determined by flow cytometry and measured as oxidative burst. The cellular oxidative burst induced by the particles was higher for end-group uncapped polymers. Opsonization increased significantly the oxidative activity of J774 monocytes, but affected inconsistently that of human blood monocytes. The results demonstrate that PLA and PLGA microspheres loaded with gentamicin sulfate were efficiently phagocytosed in vitro. The end-group uncapped polymer-type microspheres promoted significantly cell activation, which may be of importance for drug delivery and targeting to intracellular infections.


Conductance volumetric model of an eccentrically positioned catheter within a three-compartment ellipsoidal ventricle.
This paper presents a mathematical model of the electric field generated and resistance measured by a conductance catheter within a three-compartment ellipsoidal approximation of a cardiac ventricle. The model is based on a novel combination of analytical and numerical techniques. The numerical component of the model predicts displacement of the catheter along the central longitudinal ventricular axis, as well as eccentric positions off that axis. The analytical component of the model enables interactive definition of model parameters during simulation. This versatile combination enables performance of validation studies that include simulations of various catheter movements within a ventricle of changing geometry. The results of our simulation studies agree with the results of previous investigators studying ex-vivo systems.


Sutureless perceval aortic valve replacement: results of two European centers.
The Perceval S bioprosthesis (Sorin Biomedica Cardio Srl, Sallugia, Italy) is a self-expanding valve designed to preserve aortic sinuses and sinotubular junction. We report the midterm results of a prospective, multicenter clinical study evaluating the safety and efficacy of this stented bioprosthesis in patients undergoing aortic valve replacement with or without concomitant procedures. From January 2007 to September 2011, a total of 208 high-risk patients (mean European system for cardiac operative risk evaluation: 8.7±5.3 years) received a Perceval bioprosthesis in 2 European centers. Median follow up was 10±20 months and 100% complete, and the total accumulated follow-up was 156 patient-years. Ten patients have reached a 4-year follow-up. Valve function was assessed in all patients. Valve implantation resulted in significant improvement of patients' symptoms. Mean preoperative and postoperative gradients were 48.6±18.6 mm Hg and 10.4±4.3 mm Hg, respectively, and preoperative and postoperative mean effective orifice areas were 0.7±0.2 and 1.4±0.4 cm2. Survival at 12 months was 87.1%, success of implantation was 95%, and freedom from reoperation was 96%. In hospital mortality was 2.4%. During follow-up, 9 patients (4%) required reoperation for paravalvular regurgitation; 7 early and 2 late reoperations. Mean cross-clamp time (CCT) and extracorporeal circulation time (ECT) were, respectively, 33±14 minutes and 54±24 minutes, including 45 patients who underwent surgery through ministernotomy. Concomitant coronary bypass was done in 48 patients with mean CCT 43±13 and ECT 68±25 minutes. Perceval sutureless is a safe bioprosthesis that can easily be implanted, including by a minimally invasive technique. It provides excellent hemodynamic with significant clinical improvement. Overall, these data confirm the safety and utility of the Perceval bioprosthesis aortic valve replacement for high-risk patients.


Environment-dependent conformation investigation of 3-amino-1,2,4-triazole (3-AT): Raman Spectroscopy and density functional theory.
In the paper, diverse tautomers of 3-amino-1,2,4-triazole (3AT) in solid and polar solvent have been explored by FT-IR, FT-Raman and 488nm Raman experiments combing with quantum chemical theoretical calculation using PCM solvent model and normal mode analysis. The vibrational spectra prefer the 3-amino-1,2,4-2H-triazole (2H-3AT) dimer in solid, while in a polar solvent 3AT is apt to the 3-amino-1,2,4-2H-triazole (2H-3AT) monomer. The significant wavenumber difference and Raman intensity patterns in solid and different solvents are induced by hydrogen bond perturbation along >NH⋯N≤ hydrogen bonds on five-membered N-heterocyclic ring. The ground state proton transfer reaction mechanism along the five-membered N-heterocyclic ring is supported by intermolecular hydrogen bonding between 3AT and protonic solvent molecules.


Late inguinal metastasis of a well-differentiated subungual squamous cell carcinoma after radical toe amputation.
Although squamous cell carcinoma (SCC) is commonly found on sun-exposed skin, this malignancy in nail beds is rare. There is a very low rate of metastases, especially for well-differentiated lesions without bony involvement. To present a case of late inguinal metastasis after radical toe amputation 3 years previously for subungual SCC. Case report. The patient received modified inguinal lymphadenectomy and adjuvant radiation therapy. No recurrence or metastases were observed for 12 months. For patients with subungual SCC postsurgery, it is important to regularly evaluate for a minimum of 3 years, despite the very low rate of metastases.


Intramedullary teratoma of the spine: report of two adult cases.
Two case reports of intramedullary teratoma in the spinal cord of adults, and a review of the literature. To investigate and describe unusual cases of spinal teratoma using MRI to define features that may be used to avoid misdiagnosis. A department of orthopedic surgery in Japan. One patient, a 37-year-old woman, was referred because of gait disturbance. She was evaluated by myelography, CT scan with myelography, and MRI. T12 through L1 laminoplasty was performed and the tumor was subtotally removed. The other patient, a 56-year-old man, was referred because of muscle weakness and sensory disturbance. MRI revealed multiple spinal tumors. C4 through C6 laminoplasty and T12 through L2 laminoplasty were performed, and the tumors in these regions were subtotally removed. In Case 1, the postoperative course was excellent, and histological examination of the resected specimen revealed a spinal teratoma consisting of ectodermal and mesodermal elements. In Case 2, the symptoms were resolved after surgery, and ectodermal, mesodermal and endodermal elements were revealed. Although intramedullary teratomas are very rare in adults, they need to be considered in differential diagnosis.


Chitosan cross-linked and grafted with epichlorohydrin and 2,4-dichlorobenzaldehyde as an efficient adsorbent for removal of Pb(II) ions from aqueous solution.
Epichlorohydrin-modified chitosan-Schiff base composite (CS/24Cl/ECH) prepared via the one-pot reaction as characterized by Fourier transform Infra-Red spectroscopy (FT-IR), X-ray powder diffraction (XRD), Differential scanning calorimetry (DSC) and Scanning electron microscope (SEM). Its removal ability of Pb(II) ions from aqueous solution was investigated. The adsorption of Pb(II) ions carried out at different initial pH, dose of CS/24-Cl/ECH, contact time and co-existing ions. The maximum adsorption capacity of Pb(II) ions was 170 mg/g. Finally, based on the absorption results, the adsorption of Pb(II) ions was fitted by single-layer Langmuir isotherm model and the pseudo-second-order (PSO) kinetics model. The absorption mechanism of Pb(II) ions was controlled by chemical coordination Pb(II) ions with the active sites on the surface of CS/24Cl/ECH composite. Also, CS/24Cl/ECH showed excellent recyclable efficiency up to 5 cycle and potential sorbent for other heavy metal ions.


Regulation of the TRP4 gene of Saccharomyces cerevisiae at the transcriptional level and functional analysis of its promotor.
The TRP4 gene of Saccharomyces cerevisiae, which encodes anthranilate phosphoribosyl transferase (E.C. 18.104.22.168), is subject to the general control of amino acid biosynthesis. The regulation takes place at the transcriptional level by increasing the amount of initiation and not by changing the stability of mRNA. We have observed a change in the utilization of TRP4 mRNA start sites, depending on whether cells were grown under repressing or derepressing conditions. The function of promoter elements has been tested by deletion analysis with a plasmid-encoded TRP4 gene. A routinely practicable method was used for copy-number calibration of plasmids based on 2 micron DNA. Promoter structures and spacing problems in the TRP4 promoter region are discussed.