A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment.
The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by in-vitro and in-vivo studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.


Homocysteine, B-vitamin supplementation, and stroke prevention: from observational to interventional trials.
Homocysteine is an amino acid, the metabolism of which is linked to that of several vitamins-especially folic acid, B6, and B12. A high concentration of homocysteine in the plasma is linked to vascular disease, including stroke. Concentrations of homocysteine can be inexpensively and safely lowered by treatment with a combination of folate, vitamin B12, and vitamin B6. However, whether the association between high plasma concentrations of homocysteine and vascular disease is causal is unclear. Two studies have assessed the relation between dietary or supplementary B vitamin intake on the risk of stroke. In a prospective observational study of 43?732 healthy men, there was an inverse relation between dietary folate intake and the risk of ischaemic stroke. The Vitamin Intervention for Stroke Prevention study (VISP) was the first large-scale randomised interventional study that investigated the lowering of homocysteine concentrations with B vitamins in patients with ischaemic stroke. There was an association between baseline homocysteine concentrations and vascular risk in this trial. Plasma concentrations of homocysteine were only modestly reduced by high-dose versus low-dose formulation, and there was no treatment effect on recurrent stroke, coronary events, or deaths. Limitations of VISP included that only patients with mild increases in baseline homocysteine concentrations were studied, only modest reductions of homocysteine concentrations were achieved, and follow up was short. In addition, fortification of food with folate and treatment of low vitamin-B12 concentrations may have masked the effect of treatment on stroke risk. WHAT NEXT?: When exposure can be safely assigned at random, as in the case of B-vitamin therapy, randomised trials should be the standard proof to determine the effect of therapy. The results of the first randomised clinical trial of B vitamins for secondary prevention of stroke were neutral. Larger trials with longer follow-up, selection of patients with higher plasma concentrations of homocysteine, and systematic assessment of cognitive functions and dementia are needed. In the meantime, homocysteine-lowering treatment that is cheap and well-tolerated should be considered a rational approach in patients at high risk of stroke and high concentrations of homocysteine.


Megakaryocytes in myelodysplasia: an immunohistochemical study on bone marrow trephines.
Megakaryocytes in 63 bone marrow trephine biopsies were examined for their staining characteristics, location and size distribution using the monoclonal antibody Y2/51 directed against platelet glycoprotein IIIa (CD61). Megakaryocytes in normal bone marrow were evenly distributed and demonstrated homogeneous staining with Y2/51. In addition, there was little variation in their size or shape. In contrast, myelodysplastic and myeloproliferative bone marrow trephines showed considerable dysmegakaryopoiesis demonstrated by heterogeneity of staining, an altered architectural distribution with a predominantly paratrabecular location and considerable variation in size and shape. Furthermore, in myelodysplasia 25% of the CD61 positive cells were micromegakaryocytes as opposed to less than 10% in normal or reactive marrows. Such dysmegakaryopoiesis is believed to be a clinically important feature of myelodysplasia, although until now it has only been possible to assess it subjectively. The availability of the monoclonal antibody Y2/51 provides a rapid and reproducible means of studying megakaryocyte size, shape and distribution in routine trephine specimens and may help to overcome some of the diagnostic problems currently associated with myelodysplasia and other intrinsic bone marrow neoplasias.


A Systematic Review of Integrated Care Interventions Addressing Perinatal Depression Care in Ambulatory Obstetric Care Settings.
This systematic review searched 4 databases (PubMed/MEDLINE, Scopus, CINAHL, and PsychINFO) and identified 21 articles eligible to evaluate the extent to which interventions that integrate depression care into outpatient obstetric practice are feasible, effective, acceptable, and sustainable. Despite limitations among the available studies including marked heterogeneity, there is evidence supporting feasibility, effectiveness, and acceptability. In general, this is an emerging field with promise that requires additional research. Critical to its real-world success will be consideration for practice workflow and logistics, and sustainability through novel reimbursement mechanisms.


A multidisciplinary approach: Case report of an abdominal aortic aneurysm with type IIIA endoleak in the setting of cholangitis.
Endoleaks are a common complication of endovascular aortic aneurysm repair and often lead to aneurysm rupture. We report a complex case of a Type IIIA endoleak in a patient with suspected cholangitis. Immediate surgical measures to manage both the cholangitis and endoleak were performed while minimizing the risk of graft infection.


Stability and bioaccessibility of β-carotene in nanoemulsions stabilized by modified starches.
Oil-in-water nanoemulsions stabilized by food-grade biopolymer emulsifiers (modified starches) were fabricated using high-pressure homogenization in an effort to improve the stability and bioaccessibility of β-carotene. Physicochemical and biological properties of β-carotene nanoemulsions were investigated considering the particle size, β-carotene retention, and in vitro digestion. During 30 days of storage at different conditions, the mean diameters of the emulsion systems were increased by 30-85%. The retention of β-carotene in nanoemulsions was significantly higher compared to that of the β-carotene dispersed in bulk oil. After in vitro digestion, the bioaccessibility of β-carotene was increased from 3.1% to 35.6% through nanoencapsulation. The results also indicated that modified starch with high dispersed molecular density led to a higher retention but lower bioaccessibility of β-carotene in nanoemulsions. This could be due to the thick and dense interfacial layer around the oil droplets. This result provides useful information for developing protection and delivery systems for carotenoids.


Nursing concept analysis in North America: state of the art.
The strength of a discipline is reflected in the development of a set of concepts relevant to its practice domain. As an evolving professional discipline, nursing requires further development in this respect. Over the past two decades in North America there have emerged three different approaches to concept analysis in nursing scholarship: Wilsonian-derived, evolutionary, and pragmatic utility. The present paper compares and contrasts these three methods of concept in terms of purpose, procedures, philosophical underpinnings, limitations, guidance for researchers, and ability to contribute to nursing knowledge and disciplinary advancement. This work extends prior criticisms of concept analysis methods, especially as formulated by Morse and colleagues, by promoting further critical discussion regarding the direction and effectiveness of nursing efforts to meet the basic needs of disciplinary development. Its central thesis is that nursing concept analysis must advance beyond the Wilsonian-derived methods of Walker and Avant by devoting greater attention to understanding the domain of concepts to be analysed and deriving features from these contexts.


[Impact of dose boost in skull base on recurrence of stage T4 nasopharyngeal carcinoma].
The recurrence rate in skull base is high for nasopharyngeal carcinoma (NPC) patients with cavernous sinus or/and sphenoid sinus involvement. This study was conducted to explore the impact of dose boost in skull base on the recurrence in skull base and survival of NPC patients with cavernous sinus or/and sphenoid sinus involvement. A total of 120 stage T4 NPC patients with cavernous sinus or/and sphenoid sinus involvement proved by histopathology and computed tomography (CT) were treated in our hospital from Oct. 1996 to Nov. 1998. The irradiation dose was (71.55+/-3.09) Gy in nasopharynx and (58.95+/-6.16) Gy in neck. Of the 120 patients, 27 received irradiation (6-10 Gy) in skull base after radiotherapy (boost group), 93 did not receive irradiation in skull base (control group). Fifty-three patients, 41 in control group and 12 in boost group, received cisplatin-based chemotherapy for 1-3 cycles. The survival rates and the recurrence of the 2 groups were calculated by Kaplan-Meier method and log-rank test. The clinical characteristics of patients were similar in the 2 groups. The 1-, 3-, 5-year skull base control rates were significantly higher in boost group than in control group (100% vs. 93.4%, 91.8% vs. 76.4%, and 86.8% vs. 65.1%, respectively, P=0.045). The 1-, 3-, 5-year disease-freely survival rates were slightly higher in boost group than in control group (85.2% vs. 75.3%, 59.3% vs. 45.2%, and 51.9% vs. 31.2%, respectively, P=0.084). The median disease-freely survival time was longer in boost group than in control group (60 months vs. 30 months). The prevalences of irradiation-induced brain damage were 7.4% in boost group and 4.3% in control group with no significant difference (P=0.514). Dose boost in skull base can reduce the recurrence of stage T4 NPC in skull base and tends to enhance the disease-freely survival rate for NPC patients with cavernous sinus or/and sphenoid sinus involvementû it is recommended to such patients.


[What is new in surgery for primary hyperparathyroidism?].
Primary hyperparathyroidism is being increasingly recognized because of the widespread availability of biological screening, thus explaining that one third of the patients are nowadays asymptomatic at diagnosis. Initially based on the hypercalcemia-hypophosphoremia syndrome, its diagnosis is now depending upon biological measurements of AMPc, intact (1-84) parathyroid hormone and dynamic tests such as the oral calcium-loading test. A controversial issue is the use of sophisticated imaging methods (ultrasonography, computed tomography, thallium-technetium scanning, magnetic resonance imaging and more infrequently venous catheterization with blood sampling) to localize the abnormal parathyroid glands, which are clearly inferior to surgery with a 95% success rate. The lesions include single adenoma in 80%, multiple adenomas in 5%, cancer in 1% and hyperplasia in 14% of the cases. Moreover, among the majority of seemingly sporadic hyperparathyroidism, about 10% of the cases appear to be part of a multiple endocrine neoplasia which is frequently misdiagnosed or lately recognized. The questions remain (as to) whether the surgical strategy should be revisited and whether intraoperative histopathological examination of the removed abnormal gland is still needed to ensure excellence in the management of hyperparathyroidism. However, since its initial description in the early 80s, the concept of unilateral cervical exploration directed by an accurate localization study and intraoperative measurements of intact hormone could become in the future the standard approach for surgical treatment in more than half of the patients.


[Study of normal and pathological keratinization using anti-keratin polypeptide sera (author's transl)].
Anti-keratin polypeptide sera were obtained against the different bands of polyacrylamide gel electrophoresis of fibrous proteins of stratum corneum derived from normal human epidermis. The sera were tested by indirect immunofluorescence of immunoperoxidase techniques. It was demonstrated that antibodies against P1 and P2 polypeptides, of MW 67,000 and 62,000 daltons respectively, were directed towards cytoplasmic antigens of keratinocytes of the upper Malpighian layers, while no labelling could be detected in the basal cell layer. Anti-P3 polypeptide sera and the anti-whole keratin serum labelled the whole epidermis, including the basal cell layer. Ultrastructural immuno-labelling performed on free epidermal cells obtained after trypsinization demonstrated that receptors for anti-P1 polypeptide sera were tonofilaments. These results showed that some keratin components (P1 and P2 polypeptides) might be absent in basal cell tonofilaments. This in in favour of various differentiation stages of the keratinizing cells. Keratin polypeptide 1 could be a useful marker of keratinization. According to preliminary studies, the expression of this keratin antigens was markedly disturbed in tumors such as basal and squamous cell carcinoma, in warts and in ichthyosis.


Sulfated ferulic acid is the main in vivo metabolite found after short-term ingestion of free ferulic acid in rats.
The bioavailability of ferulic acid (FA; 3-methoxy-4-hydroxycinnamic acid) and its metabolites was investigated in rat plasma and urine after an oral short-term ingestion of 5.15 mg/kg of FA. Free FA, glucuronoconjugates, and sulfoconjugates were quickly detected in plasma with a peak of concentration found 30 min after ingestion. Sulfoconjugates were the main derivates ( approximately 50%). In urine, the cumulative excretion of total metabolites reached a plateau 1.5 h after ingestion, and approximately 40% were excreted by this way. Free FA recovered in urine represented only 4.9 +/-1.5% of the native FA consumed by rats. Glucuronoconjugates and sulfoconjugates represented 0.5 +/- 0.3 and 32.7 +/- 7.3%, respectively. These results suggested that a part of FA incorporated in the diet was quickly absorbed and largely metabolized in sulfoconjugates before excretion in urine.


Lateral Gene Transfer in the Adaptation of the Anaerobic Parasite Blastocystis to the Gut.
Blastocystis spp. are the most prevalent eukaryotic microbes found in the intestinal tract of humans. Here we present an in-depth investigation of lateral gene transfer (LGT) in the genome of Blastocystis sp. subtype 1. Using rigorous phylogeny-based methods and strict validation criteria, we show that ∼2.5% of the genes of this organism were recently acquired by LGT. We identify LGTs both from prokaryote and eukaryote donors. Several transfers occurred specifically in ancestors of a subset of Blastocystis subtypes, demonstrating that LGT is an ongoing process. Functional predictions reveal that these genes are involved in diverse metabolic pathways, many of which appear related to adaptation of Blastocystis to the gut environment. Specifically, we identify genes involved in carbohydrate scavenging and metabolism, anaerobic amino acid and nitrogen metabolism, oxygen-stress resistance, and pH homeostasis. A number of the transferred genes encoded secreted proteins that are potentially involved in infection, escaping host defense, or most likely affect the prokaryotic microbiome and the inflammation state of the gut. We also show that Blastocystis subtypes differ in the nature and copy number of LGTs that could relate to variation in their prevalence and virulence. Finally, we identified bacterial-derived genes encoding NH3-dependent nicotinamide adenine dinucleotide (NAD) synthase in Blastocystis and other protozoan parasites, which are promising targets for drug development. Collectively, our results suggest new avenues for research into the role of Blastocystis in intestinal disease and unequivocally demonstrate that LGT is an important mechanism by which eukaryotic microbes adapt to new environments.


Conservation of wild animals by assisted reproduction and molecular marker technology.
Wild animals are an integral component of the ecosystem. Their decimation due to abrupt natural calamities or due to gradual human intervention would be disastrous to the ecosystem and would alter the balance in nature between various biotic components. Such an imbalance could have an adverse effect on the ecosystem. Therefore, there is an urgent need to put an end to the ever increasing list of endangered species by undertaking both in situ and ex situ conservation using tools of modern biology, to ascertain the degree of genetic variation and reproductive competence in these animals. This review highlights the development and use of molecular markers such as microsatellites, minisatellites, mitochondrial control region, cytochrome b and MHC loci to assess the genetic variation in various Indian wild animals such as the lion, tiger, leopard and deer. The review also presents data on the semen profile of the big cats of India. Reproductive technologies such as cryopreservation of semen and artificial insemination in big cats are also highlighted.


Interactions between health technology assessment, coverage, and regulatory processes: emerging issues, goals, and opportunities.
The relationship between regulatory approval on the one hand and health technology assessment (HTA) and coverage on the other is receiving growing attention. Those responsible for regulatory approval, HTA, and coverage have different missions and their information requirements reflect these. There is nonetheless an increasingly popular view that improved communication and coordination between these functions could allow them all to be undertaken effectively with a lower overall burden of evidence requirements, thus speeding patient access to new products and reducing unnecessary barriers to innovation. This study summarizes the main points emerging from a recent discussion of this topic at the HTAi Policy Forum. After considering the roles of the various bodies, stakeholder perspectives and some current practical initiatives, those present at the Forum meeting discussed possible goals and challenges for improved interactions-in general and at specific stages of the product development life cycle. Opportunities for progress were seen in: continuing the dialogue to promote understanding and interaction between the different bodies and stakeholders; working to align scientific advice for manufacturers on the design and data requirements of pre- and post-marketing evaluation of products (specifically phase 2/3 and phase 4 trials for drugs); and extending the current dialogue to include discussion of product development to address unmet health needs.


Safety and feasibility of orbital atherectomy for the treatment of calcified coronary lesions: the ORBIT I trial.
The ORBIT I trial evaluated the safety and performance of an orbital atherectomy system (OAS) for the treatment of de novo calcified coronary lesions. Severely calcified coronary arteries pose an ongoing treatment challenge. Stent placement in calcified lesions can result in stent under expansion, malapposition, and procedural complications. OAS treatment may change calcified lesion compliance to reduce procedural complications and facilitate stent placement. The ORBIT I trial, a prospective, nonrandomized study, was conducted in two centers in India. Fifty patients with de novo calcified coronary lesions were enrolled. Patients were treated with the OAS followed by stent placement. The average age of the patients was 57.4 years and 90% were male. Mean lesion length was 13.4 mm. The average number of OAS devices used per patient was 1.3. Device success was 98%, and procedural success was 94%. The cumulative major adverse cardiac event rate was 4% in-hospital (two non-Q-wave myocardial infarctions), 6% at 30 days (one additional non-Q-wave myocardial infarction leading to target lesion revascularization), and 8% at 6 months (one additional event of cardiac death). Angiographic complications were observed in seven patients (six dissections and one perforation). The ORBIT I trial suggests that the OAS may offer an effective method to change compliance of calcified coronary lesions to facilitate optimal stent placement in these difficult to treat patients. A larger trial is required to establish safety and overall effectiveness of the OAS in treating calcified coronary lesions.


Benzimidazole nitrogen-directed, regiocontrolled, lithiation of ferrocenyl- and phenyl-N-n-butylbenzimidazoles.
2-Ferrocenyl- and 2-phenyl-N-n-butylbenzimidazoles were synthesized to evaluate the influence of the benzimidazole functional group upon their directed lithiation. The regiochemistry of lithiation was studied, as well as the effect of stabilization of the lithiated species by diamine coordination using tetramethyl- ethylenediamine and (-)-sparteine. The lithiations were followed by reaction with a variety of electrophiles to give the disubstituted 2-ferrocenyl- and 2-phenyl-N-n-butylbenzimidazoles compounds. This study showed that despite a simple n-butyl function on the benzimidazole, directed lithiation was readily achieved with high regiocontrol on the ferrocenyl and phenyl groups. (-)-Sparteine failed to provide asymmetric induction in the ferrocene system, and its inefficiency is explained by intramolecular coordination of the lithiated species by the benzimidazole nitrogen, which is preferred over sparteine coordination.


Improving the quality of near-patient blood glucose measurement.
The quality of near-patient blood glucose measurement was audited in our hospitals in 1990, when a diversity of glucose meters were in use, by sending three samples of unknown (to the meter user) concentration to each user and collecting and analysing the results produced. The overall performance was unsatisfactory with a mean coefficient of variation (CV) of 23.5%. A scheme involving training, quality control and external quality assurance was introduced in 1993 based on the Bayer Glucometer II meter. This meter was used exclusively throughout our hospitals. Data from the quality assurance scheme showed that the overall CV fell initially to 14-16% and then settled at about 10-12% for the following 2 years. Unacceptable results (those more than two standard deviations from the mean) were 8-12% of the total. A new meter was introduced in 1995 (the Bayer Glucometer 4) which had the advantages of 'no-wipe' and automatic timing technology and in the subsequent year overall CV fell to 5-6% and has remained at this level. The frequency of unacceptable results fell to 5-7%. The improved precision figures encouraged us to change criteria for acceptability to mean +/- 15%. Using these criteria the level of unacceptable results is now 1-2%. This study shows that introducing training, quality control procedures, a quality assurance scheme and improved meter technology all backed by laboratory expertise can produce significant improvement in the quality of near patient blood glucose measurement.


Health-related behaviours and weight status of expectant fathers.
Little attention has been given to the health status and lifestyle behaviours of expectant fathers. This study aimed to examine health-related variables in a cohort of expectant fathers to identify potential focus areas for interventions designed to optimise health and wellbeing outcomes in this group. Partners of pregnant women who accessed antenatal services at a large maternity unit in a Western Australian hospital were recruited as part of the ORIGINS Project. Analyses were conducted on data from 498 expectant fathers who were primarily of mid and high socioeconomic status. Participants reported relatively low levels of smoking and alcohol consumption and higher physical activity compared to national averages. Weight status was consistent with population norms for adult males: 76% were overweight or obese and 62% had a waist girth ≥94cm. Expectant fathers may benefit from health interventions, especially in relation to managing their weight during this phase of their lives and beyond. Pregnancy represents a valuable opportunity to engage fathers-to-be in health interventions. Given identified links between paternal weight status and offspring outcomes, interventions focusing on achieving and maintaining a healthy weight among expectant fathers could be beneficial for families.


Oral contraceptive use and the ECG: evidence of an adverse QT effect on corrected QT interval.
A prolonged corrected QT (QTc) interval is a marker for an increased risk of sudden cardiac death. We evaluated the relationship between oral contraceptive (OC) use, type of OC, and QTc interval. We identified 410,782 ECGs performed at Northern California Kaiser Permanente on female patients between 15 and 53 years from January, 1995 to June, 2008. QT was corrected for heart rate using log-linear regression. OC generation (first, second and third) was classified by increasing progestin androgenic potency, while the fourth generation was classified as antiandrogenic. Among 410,782 women, 8.4% were on OC. In multivariate analysis after correction for comorbidities, there was an independent shortening effect of OCs overall (slope = -0.5 ms; SE = 0.12, P < 0.0002). Users of first and second generation progestins had a significantly shorter QTc than nonusers (P < 0.0001), while users of fourth generation had a significantly longer QTc than nonusers (slope = 3.6 ms, SE = 0.35, P < 0.0001). Overall, OC use has a shortening effect on the QTc. Shorter QTc is seen with first and second generation OC while fourth generation OC use has a lengthening effect on the QTc. Careful examination of adverse event rates in fourth generation OC users is needed.


Lattice continuum and diffusional creep.
Diffusional creep is characterized by growth/disappearance of lattice planes at the crystal boundaries that serve as sources/sinks of vacancies, and by diffusion of vacancies. The lattice continuum theory developed here represents a natural and intuitive framework for the analysis of diffusion in crystals and lattice growth/loss at the boundaries. The formulation includes the definition of the Lagrangian reference configuration for the newly created lattice, the transport theorem and the definition of the creep rate tensor for a polycrystal as a piecewise uniform, discontinuous field. The values associated with each crystalline grain are related to the normal diffusional flux at grain boundaries. The governing equations for Nabarro-Herring creep are derived with coupled diffusion and elasticity with compositional eigenstrain. Both, bulk diffusional dissipation and boundary dissipation accompanying vacancy nucleation and absorption, are considered, but the latter is found to be negligible. For periodic arrangements of grains, diffusion formally decouples from elasticity but at the cost of a complicated boundary condition. The equilibrium of deviatorically stressed polycrystals is impossible without inclusion of interface energies. The secondary creep rate estimates correspond to the standard Nabarro-Herring model, and the volumetric creep is small. The initial (primary) creep rate is estimated to be much larger than the secondary creep rate.


Diagnostic approaches to parotid swellings.
Although the mainstay assessment of parotid swellings remains clinical examination, cytology, computed tomography and magnetic resonance imaging may give valuable preoperative information on both the likely histology and the location of the individual swelling. This is important for therapeutic and prognostic reasons.


Flap reconstruction following wide local excision for primary malignant melanoma of the head and neck region.
There has been an increase in the incidence of malignant melanomas over the past few decades. Wide excisions of melanomas of the face may result in significant deformities if covered by skin grafts. We treated 36 consecutive patients with skin flap coverage over the last decade and report the safety, versatility, and cosmetic appeal of this technique.


Rating of perceived effort but relative to what? A comparison between imposed and self-selected anchors.
Collecting reliable and valid rating of perceived effort (RPE) data requires properly anchoring the scales' upper limits (i.e., the meaning of 10 on a 0-10 scale). Yet, despite their importance, anchoring procedures remain understudied and theoretically underdeveloped. Here we propose a new task-based anchoring procedure that distinguishes between imposed and self-selected anchors. In the former, researchers impose on participants a specific task as the anchor; in the latter, participants choose the most effortful task experienced or imaginable as the anchor. We compared the impact of these conceptually different anchoring procedures on RPE. Twenty-five resistance-trained participants (13 females) attended a familiarization and two randomized experimental sessions. In both experimental sessions, participants performed non-fatiguing and fatiguing isometric maximal voluntary contraction (MVC) protocols with the squat followed by the gripper or vice versa. After each MVC, participants reported their RPE on a 0-10 scale relative to an imposed anchor of the performed task (e.g., gripper MVCs anchored to a gripper MVC) or to a self-selected anchor. In the non-fatiguing condition, imposed anchors yielded greater RPEs than self-selected anchors for both the squat [on average, 9.4 vs. 5.5; Δ(CI95%) = 3.9 (3.2, 4.5)] and gripper [9.4 vs. 3.9; Δ = 5.5 (4.7, 6.3)]. Similar results were observed in the fatiguing condition for both the squat [9.7 vs. 6.9; Δ = 2.8 (2.1, 3.5)] and gripper [9.7 vs. 4.5; Δ = 5.2 (4.3, 5.9)]. We found large differences in RPE between the two anchors, independent of exercises and fatigue state. These findings provide a basis for further development and refinement of anchoring procedures and highlight the importance of selecting, justifying, and consistently applying the chosen anchors.


The hand knows something that the eye does not: reaching movements resist the Müller-Lyer illusion whether or not the target is foveated.
Previous reports suggest that saccades are affected by the Müller-Lyer (ML) pictorial illusion, whereas reaching movements are not. It is unclear if the resistance of reaching to illusions depends on the concurrent engagement of the oculomotor system. Here we show that the endpoints and kinematics of reaching movements were unaffected by a peripherally viewed ML stimulus regardless of whether or not a concurrent saccade was carried out. Primary saccade endpoints were affected by the ML stimulus but secondary saccades were not. Perceptual judgments of target location were influenced by the ML stimulus in the expected direction. The resistance of reaching movements to pictorial illusions does not appear to depend on the concurrent engagement of the oculomotor system. Implications for models of oculomotor and upper limb control are discussed.


Three-dimensional reconstruction of the below-knee amputation stump: use of the combined scapular/parascapular flap.
The technique of combined scapular/parascapular reconstruction of the below-knee stump wound allows three-dimensional contouring of fasciocutaneous tissue into a conical shape. The flap can supply durable cover to the circumference of the stump with good functional results. This technique should be considered for reconstruction of extensive circumferential defects of the below-knee stump.


A kindred with hemoglobin Lepore.
Four members from three generations of a family of Italian descent were found to have hemoglobin (Hb) Lepore trait. The four affected members were only slightly anemic, yet had definite hypochromic and microcytic red blood cells (RBC). Electrophoresis of hemoglobin demonstrated an abnormal non-sickling hemoglobin of 11% to 14% concentration that migrated like Hb S at alkaline pH. Amino acid analysis confirmed the identity of the abnormal component as Hb Lepore; the non-alpha chain was a fused delta-beta-chain with a crossover between residues 87 and 116. Hemoglobin Lepore trait should be considered in any patients with clinical and laboratory findings consistent with beta-thalassemia trait and with a 10% to 15% concentration of an abnormal nonsickling hemoglobin that migrates like Hb S.


[Acute peritoneal tuberculosis in HIV-infected patients. Study of 4 cases in Abidjan, Côte-d'Ivoire].
This paper presents 4 cases of histologically verified peritoneal tuberculosis in HIV-infected patients followed in a 18 month-period. The patients were admitted in emergency and were suspected of present acute appendiceal peritonitis. There were 3 females of 18, 22 and 27 years old, and a 41-year-old male. The main symptoms were acute abdominal pain (4 cases), fever superior to 38 degrees C (4 cases) and abdominal defence (4 cases). Laboratory findings were hyperleucocytosis with lymphocytic predominance, anemia and CD4+ rate variable from 250 to 460/mm3. They underwent emergency laparotomy which led to diagnosis of peritoneal tuberculosis by histopathological analysis of peritoneal biopsies. Two patients died from surgery at days 3rd and 10th. The 2 remaining patients were successfully treated by tuberculostatic tritherapy with rifampicin, isoniazid, and pirazinamid. Acute peritoneal tuberculosis in HIV-infected patients is not to be missed in our practice. It must be considered in differential diagnosis of acute abdomens.


Contrast Challenge Algorithms for Adhesive Small Bowel Obstructions Are Safe in Children: A Multi-Institutional Study.
The purpose of this study was to evaluate the safety of a water-soluble contrast challenge as part of a nonoperative management algorithm in children with an adhesive small bowel obstruction (ASBO). Predicting which children will successfully resolve their ASBO with non-operative management at the time of admission remains difficult. Additionally, the safety of a water-soluble contrast challenge for children with ASBO has not been established in the literature. A retrospective review was performed of patients who underwent non-operative management for an ASBO and received a contrast challenge across 5 children's hospitals between 2012 and 2020. Safety was assessed by comparing the complication rate associated with a contrast challenge against a pre-specified maximum acceptable level of 5%. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of a contrast challenge to identify successful nonoperative management were calculated. Of 82 children who received a contrast challenge, 65% were successfully managed nonoperatively. The most common surgical indications were failure of the contrast challenge or failure to progress after initially passing the contrast challenge. There were no complications related to contrast administration (0%; 95% confidence interval: 0-3.6%, P = 0.03). The contrast challenge was highly reliable in determining which patients would require surgery and which could be successfully managed non-operatively (sensitivity 100%, specificity 86%, NPV 100%, PPV 93%). A contrast challenge is safe in children with ASBO and has a high predictive value to assist in clinical decision-making.


In silico search of inhibitors of Streptococcus mutans for the control of dental plaque.
Biofilm is an extremely complex microbial community arranged in a matrix of polysaccharides and attached to a substrate. Its development is crucial in the pathophysiology of oral infections like dental caries, as well as in periodontal, pulp, and periapical diseases. Streptococcus mutans is one of the most effective microorganisms in lactic acid production of the dental biofilm. Identifying essential Streptococcus mutans proteins using bioinformatics methods helps to search for alternative therapies. To this end, the bacterial genomes of several Streptococcus mutans strains and representative strains of other cariogenic and non-cariogenic bacteria were analysed by identifying pathogenicity islands and alignments with other bacteria, and by detecting the exclusive genes of cariogenic species in comparison to the non-pathogenic ones. This study used tools for orthology prediction such as BLAST and OrthoMCL, as well as the server IslandViewer for the detection of pathogenicity islands. In addition, the potential interactome of Streptococcus mutans was rebuilt by comparing it to interologues of other species phylogenetically close to or associated with cariogenicity. This protocol yielded a final list of 20 proteins related to potentially virulent factors that can be used as therapeutic targets in future analyses. The EIIA and EIIC enzymatic subunits of the phosphotransferase system (PTS) were prioritized, as well as the pyruvate kinase enzyme, which are directly involved in the metabolism of carbohydrates and in obtaining the necessary energy for the microorganism's survival. These results will guide a subsequent experimental trial to develop new, safe, and effective molecules in the treatment of dental caries.


[Comparison of neonatal mortality in very low birth weight newborns at maternity hospitals in the city of Rio de Janeiro, Brazil].
This study was a comparison of neonatal mortality rates in four maternity hospitals in the city of Rio de Janeiro, Brazil. The study population consisted of newborns with birth weight below 1,500 g. The research instrument was a questionnaire with data reported by the mother and collected from the patient record. For each maternity hospital the standardized mortality ratio (SMR) was calculated using the direct and indirect method, using the weight distribution of the National Institute of Child Health and Human Development Neonatal Research as the standard. The final sample consisted of 487 newborns. Standardizations by the direct and indirect method showed high mortality rates in all four institutions; those showing the largest number of newborns in the lowest weight brackets were those with the lowest SMR values. The lowest mortality ratio by weight bracket was in the 500 to 749 g group. The SMR results were inversely associated with the quantitative population of newborns in the lowest weight brackets. The mortality coefficients showed high rates, especially in the highest weight brackets. The results indicate deficient quality of perinatal care.


Skeletal muscle microvascular alterations in euthyroid and hypothyroid patients with autoimmune thyroid disease.
An electron microscopic study of skeletal muscle biopsies from euthyroid and hypothyroid patients with autoimmune thyroid disease (ATD) showed the existence of capillary alterations and a mononuclear cell infiltrate. Microvascular abnormalities included thickening and lamination of basement membrane, endothelial proliferation with progressive lumen occlusion, and hypertrophied pericytes. Capillary degeneration was also observed. Macrophages, and scarce lymphocytes and mast cells formed the cell infiltrate. This pathological picture is similar to that found in the muscular compromise of other autoimmune diseases, particularly Graves' hyperthyroidism. This study shows that patients with ATD may have skeletal muscle capillary abnormalities that could probably be related to autoimmunity and are independent of thyroid functional status.


Immune responses in 4-1BB (CD137)-deficient mice.
The 4-1BB (a TNFR superfamily member) is an inducible costimulatory molecule that can exert regulatory effects on T cells independently of CD28 stimulation. The in vitro expression of 4-1BB (CD137) is induced following activation of T cells with various stimuli, including anti-TCR mAbs, lectins, and a combination of PMA and ionomycin. To delineate further the physiological role of 4-1BB in immunity, mice deficient in this receptor were generated. These mutant mice developed normally, and were viable and fertile. Humoral responses to vesicular stomatitis virus were comparable with those seen in wild-type mice, whereas the IgG2a and IgG3 isotype responses to keyhole limpet hemocyanin were somewhat reduced in the mutant mice. The 4-1BB-deficient mice demonstrated enhanced T cell proliferation in response to mitogens or anti-CD3 even in the environment of reduced ability to secrete growth-supporting cytokines (IL-2 and IL-4). Although T cells from 4-1BB-deficient mice showed enhanced proliferation, the T cell immune responses of these animals, such as cytokine production and CTL activity, were diminished. In addition, 4-1BB deletion appears to play a role in the regulation of myeloid progenitor cell growth, leading to an increase in these precursor cells in peripheral blood, bone marrow, and spleen.


Exposure to Bisphenolic Analogues in the Sixth Total Diet Study - China, 2016-2019.
Bisphenol A (BPA) and other bisphenolic compounds (BPs) are proved to pose potential endocrine disrupting properties. The primary source of BP exposure is the diet. European Food Safety Authority (EFSA) established a temporary tolerable daily intake (t-TDI) of BPA 4 μg/kg body weight per day. BPs were detected in composite food samples from the Sixth China Total Diet Study (TDS) at percentages of 27.1%-78.5%. The estimated dietary exposure of BPA and bisphenol S (BPS) for an average adult were 18.1 ng/kg body weight per day and 22.2 ng/kg body weight per day, respectively. The main dietary contributors for BPs were cereals, water and beverage, meat as well as vegetables. BP dietary intake poses low risks on the Chinese general population based on the t-TDI set by EFSA. BPS presented a higher exposure level than BPA, which highlights the need to strengthen the surveillance of BP alternatives in foodstuffs.


Inotuzumab ozogamicin in the treatment of acute lymphoblastic leukemia.
Antibody-drug conjugates (ADCs) represent a major advance in the treatment of acute lymphoblastic leukemia (ALL). CD22 expression, seen in majority of patients with B-lineage ALL, is an ideal target for ADCs. Inotuzumab ozogamicin is an ADC comprised of a humanized IgG4 monoclonal antibody covalently linked to calecheamicin. Inotuzumab ozogamicin has shown promising single-agent activity in patients with ALL and in CD22 positive non-Hodgkin lymphoma. Studies exploring the combination of inotuzumab ozogamicin with chemotherapy are ongoing.


The proteome of exudates from germinating Lupinus albus seeds is secreted through a selective dual-step process and contains proteins involved in plant defence.
The general knowledge of defence activity during the first steps of seed germination is still largely incomplete. The present study focused on the proteins released in the exudates of germinating white lupin seeds. During the first 24 h, a release of proteins was observed. Initially (i.e. during the first 12 h), the proteins found in exudates reflected the composition of the seed, indicating a passive extrusion of pre-formed proteins. Subsequently, when the rate of protein release was at its highest, the composition of the released proteome changed drastically. This transition occurred in a short time, indicating that more selective and regulated events, such as secretory processes, took place soon after the onset of germination. The present study considered: (a) the characterization of the proteome accumulated in the germinating medium collected after the appearance of the post-extrusion events; (b) the biosynthetic origin and the modalities that are the basis of protein release outside the seeds; and (c) an assessment of antifungal activity of these exudates. The most represented protein in the exudate was chitinase, which was synthesized de novo. The other proteins are involved in the cellular mechanisms responding to stress events, including biotic ones. This exudate was effectively able to inhibit fungal growth. The results of the present study indicate that seed exudation is a dual-step process that leads to the secretion of selected proteins and thus is not a result of passive leakage. The released proteome is involved in protecting the spermosphere environment and thus may act as first defence against pathogens.


Management of the neurogenic bowel in patients with spinal cord injury.
Bowel dysfunction in patients with spinal cord injury has a significant impact on quality of life as well as causing morbidity and death. This article reviews the pathophysiologic features of the neurogenic bowel of patients with spinal cord injury. Also discussed are the clinical manifestations, current options for management, and newer approaches that address this chronic and debilitating problem.


R5020 and RU486 act as progesterone receptor agonists to enhance Sp1/Sp4-dependent gene transcription by an indirect mechanism.
It has been suggested that ligand-dependent gene activation by the progesterone receptor (PR) can result from recruitment of PR by the promoter bound Sp1. A detailed investigation of the Sp1-dependent agonistic activity of RU486 and R5020 on the folate receptor (FR) type alpha, p27, thymidine kinase 1 and p21 genes reveals a different mechanism. The FR-alpha P4 promoter and the endogenous FR-alpha gene were up-regulated by the PR agonist R5020 through either PR-A or PR-B. The classical antagonist RU486 also activated the promoter but only through PR-B. The most proximal (essential) G/C-rich (Sp1 binding) element and the initiator region constituted the minimal promoter responsive to PR regulation; substitution with a stronger cluster of G/C-rich elements enhanced the magnitude of the PR response. In contrast, substitution of the G/C-rich element with a TATA box resulted in the loss of regulation by PR. Overexpression of Sp1 and Sp4 but not Sp3 enhanced activation of the FR-alpha promoter by PR, knocking down Sp1 decreased the activation in a manner that was reversed by ectopic Sp1 or Sp4. The ligand-dependent action of PR on the promoter was delayed compared with its activation of a classical glucocorticoid response element-driven promoter and activation of both the promoter and the endogenous FR-alpha gene by PR required new protein synthesis. Activation by PR paralleled RNA polymerase II recruitment but was not accompanied by either association of PR or a change in the association of Sp1 with the endogenous FR-alpha P4 promoter. Similar observations were made for PR regulation of the genes encoding p27, thymidine kinase 1, and p21. The results contradict the current view of Sp1-dependent gene regulation by PR and point to the existence of one or more PR target genes whose promoter and cell context(s) must thus be key determinants of the agonistic activity of RU486 on a large group of important Sp1-dependent downstream target genes.


The effect of aerosol hair spray inhalation in the hamster.
Hamsters were exposed to a commercially available aerosol hair spray actuated for a total of 8 minutes over a 4-hour-period, 5 days/week. They were examined after 1, 2, 3, 4, and 6-week exposures, and 2,4 and 8 weeks after a 6-week exposure. There was a significant increase in the lung weight of exposed hamsters at every time point except 8 weeks after the 6-week exposure. Microscopic changes in the lung were characterized by the presence of a few to a moderate number of macrophages and neutrophils in the alveolar lumina. The number of macrophages and neutrophils appeared directly related to the duration of exposure. Lung changes were minimal during the first 2-weeks of exposure, and 8 weeks after the 6-week exposure (recovery period). Pathologic changes in the lungs of hamsters were reversible after cessation of the hair spray inhalation exposure.


Reverse transcriptase.RNase H from the human immunodeficiency virus. Relationship of the DNA polymerase and RNA hydrolysis activities.
Human immunodeficiency virus reverse transcriptase.RNase H (RT.RNase H) has an RNA hydrolysis specificity which was influenced both by the sequence of the DNA primer-RNA template and by binding of the polymerase active site to the primer 3' terminus. RT.RNase H selectively hydrolyzed the phosphodiester bond between the 15th and 16th ribonucleotide back from the ribonucleotide that is complementary to the primer 3'-terminal deoxynucleotide. The cleavage site for RT.RNase H remained a fixed distance behind the 3'-primer terminus as the polymerase extended the primer. This cleavage was not strongly affected by the position of the DNA primer on the template nor was it affected by reducing the primer length from 40 to 25 nucleotides. These results suggest that the distance between the RNase H and polymerase active sites corresponds to the length of a 15-16-nucleotide DNA-RNA heteroduplex. Since one helical turn is approximately 10 nucleotides, the distance between the active sites is 1.5 helical turns of heteroduplex. Therefore, the two active sites (catalyzing reactions on opposite strands) bind the same side of the RNA-DNA double helix. RT.RNase H also showed some sequence dependence for the site of hydrolysis. This sequence dependence has not been fully characterized. The rate of RT.RNase H cleavage was weakly inhibited by the next coded deoxynucleoside triphosphate following the incorporation of a dideoxynucleotide.


The synthesis and applications of a micro-pine-structured nanocatalyst.
Dendritic nanoferrites with a micro-pine morphology have been synthesized for the first time under microwave irradiation conditions without using any reducing or capping reagent; the nanoferrites were then functionalized and coated with Pd metal, which catalyzes various organic transformations.


Molecular size determinations of DNA restriction fragments and polymerase chain reaction products using capillary gel electrophoresis.
Commercially available capillary electrophoresis (CE) systems offer advantages over traditional slab gel methodologies. The capillary format allows the use of higher voltages (225 V/cm), which results in faster migration, higher resolution and greater efficiency without excessive heating. The ability to automate the system increases the unattended sample analysis throughput. For this study, the CE system was configured with a muPAGE 3% T, 3% C polyacrylamide gel capillary with an effective length of 40 cm and microPAGE Tris-borate urea buffer system. The analysis of DNA restriction fragments and polymerase chain reaction products, with an internal standard of Boehringer Mannheim DNA marker XI were completed in less than 70 min. All samples were analyzed at 260 nm. The data establishes automated capillary gel electrophoresis as a high-resolution, reproducible method for analysis of samples under 1000 base pairs.


Benefits of experience. Treating coronary artery disease.
The authors examined the issue of learning by doing in terms of both the cost and outcome of treating coronary artery disease at one hospital between 1977 and 1981. Over time, the quality of outcome improved for both medical and surgical patients. During this time of cost-plus reimbursement, there was less conclusive evidence of concurrent technical efficiency gains. These findings are consistent with the hypothesis that the benefits of experience can be substantial but they do not just happen: they require proper provider motivation.


Wear of the high-density polyethylene socket in total hip arthroplasty and its role in endosteal cavitation.
High-density polyethylene (HDP) has been used in clinical practice in total hip replacement since its introduction by Charnley in November 1962. Fears are being expressed that this may be the weakest link and the ultimate cause of failure of the arthroplasty. Long-term clinical experience suggests that loosening may be the primary cause while the presence of HDP wear particles is secondary. Healing of endosteal cavities can take place in the presence of HDP wear particles.


Purification and characterization of Rpp25, an RNA-binding protein subunit of human ribonuclease P.
In HeLa cells, ribonuclease P (RNase P), the tRNA processing enzyme consists of an RNA subunit (H1 RNA) associated with at least nine protein subunits, Rpp14, Rpp20, Rpp21, Rpp29 (hPop4), Rpp30, Rpp38, Rpp40, hPop1, and hPop5 (18.8 kDa). We report here the cloning and immuno-biochemical analysis of Rpp25, another protein subunit of RNase P. Polyclonal rabbit antibodies raised against recombinant Rpp25 recognize their corresponding antigens in RNase P-containing fractions purified from HeLa cells, and they also precipitate active holoenzyme. Furthermore, this protein has general RNA binding properties.


Improving spatial data in health geographics: a practical approach for testing data to measure children's physical activity and food environments using Google Street View.
Geographic information systems (GIS) are often used to examine the association between both physical activity and nutrition environments, and children's health. It is often assumed that geospatial datasets are accurate and complete. Furthermore, GIS datasets regularly lack metadata on the temporal specificity. Data is usually provided 'as is', and therefore may be unsuitable for retrospective or longitudinal studies of health outcomes. In this paper we outline a practical approach to both fill gaps in geospatial datasets, and to test their temporal validity. This approach is applied to both district council and open-source datasets in the Taranaki region of Aotearoa New Zealand. We used the 'streetview' python script to download historic Google Street View (GSV) images taken between 2012 and 2016 across specific locations in the Taranaki region. Images were reviewed and relevant features were incorporated into GIS datasets. A total of 5166 coordinates with environmental features missing from council datasets were identified. The temporal validity of 402 (49%) environmental features was able to be confirmed from council dataset considered to be 'complete'. A total of 664 (55%) food outlets were identified and temporally validated. Our research indicates that geospatial datasets are not always complete or temporally valid. We have outlined an approach to test the sensitivity and specificity of GIS datasets using GSV images. A substantial number of features were identified, highlighting the limitations of many GIS datasets.


Relationship between the preoptico hypophysial system and the vascular system in the teleost Rita rita (Ham.).
In Rita rita the internal carotid artery gives rise to hypothalamic and hypophysial arteries. The hypophysial artery directly enters the pituitary and largely contributes to the interface vasculature lying in between the neurohypophysis and the pars distalis which can be considered as an equivalent of the median eminence. Blood vessels from the interface vasculature enter the pars distalis. The hypothalamic artery gives rise to the primary capillary plexus in the infundibular floor and the portal vessels formed by it irrigate the glandular pituitary. Both, at the level of the hypothalamus and at the interface, neurosecretory material might get access to blood vessels. Thus, in Rita rita, not only the typical teleostean type of hypothalamo-hypophysial vascularization is present, but also an incipient tetrapodal pattern is evident.


Parvovirus infection in hospital practice.
Eleven cases of human parvovirus (HPV) infection were diagnosed on the basis of positive IgM serology over a 9-month period in two London hospitals. These cases accounted for almost 30% of viral illness in which HPV serology had been requested. Ten of the cases presented with joint symptoms and/or rash and one case presented with evidence of a severe autoimmune haemolytic anaemia. Six patients had lymphadenopathy. Clinical and laboratory features of the cases are presented. HPV DNA was sought but not found in synovial fluid from one patient.


Manipulating the inorganic motif by kinetic control of antimony halide organic-inorganic hybrid materials for larger Stokes shift and significantly enhanced quantum efficiency.
Adjusting the structure of the inorganic components has been proved to be an efficient method for the performance optimization of organic-inorganic hybrid materials. One particular organic ligand can typically form numerous hybrid structures with one inorganic source; however, in most cases, only one thermodynamically stable phase can be obtained, which may not be the one with the best properties. Here, we reported a novel method for modulating the optical properties of antimony halide based organic-inorganic hybrid materials by kinetic control of the synthesis. Under such an approach, the kinetically stable phase can be synthesized, which exhibits significantly improved quantum efficiency compared to the thermodynamically stable phase. This approach provides a new route for the development of high-performance organic-inorganic hybrid materials.


The effect of Blastocystis hominis on the growth status of children.
B. hominis is a protozoan parasite commonly found in the human gastrointestinal tract. The pathogenesis of B. hominis is still controversial, although it is one of the most common parasites found in stool samples. This study was conducted at the Adnan Menderes Medical Faculty between January 2002 and June 2003 to evaluate the relationship between B. hominis and growth status in children in Aydin, Turkey. Healthy children with positive stool samples for B. hominis but negative for other parasites were selected as the case group (n=89). Two controls matched to each case by age and gender were selected by random sampling of children with negative stool samples for any parasite (n=178). The anthropometric measurements and body mass index were significantly lower in the case group than in the control group (p<0.05). According to this study there is a correlation between the presence of B. hominis and lower anthropometric indexes in children.


Evaluation of the Adherence to Immunmodulatory Treatment in Patients with Multiple Sclerosis.
In this article, we report the data regarding treatment adherence of a group of patients with multiple sclerosis (MS) and relapsing-remitting or secondary progressive disease who were followed in the MS outpatient clinic of Bozyaka Education and Research Hospital, Izmir. We collected the demographic data of 219 patients with MS who were treated with immunomodulatory drugs and the documentary data on the disease characteristics from the patient' files. Each patient was provided a detailed questionnaire regarding treatment adherence in addition to the Beck depression scale (BDS) and Paced Auditory Serial Addition Test (PASAT). Nonadherence was defined as the discontinuation of the drug, i.e., more than one dose a month for intramuscular interferon, six doses a month for glatiramer acetate, and four doses a month for subcutaneous interferons. Statistical analyses were performed using Medcalc statistics package. For those parameters with an even distribution, the paired samples t-test was used to compare the results. Of the 219 [183 relapsing remitting multiple sclerosis (RRMS) and 36 secondary progressive multiple sclerosis (SPMS)] patients included in the study, 143 patients were women and 76 were men. The mean age of the patients was 40.77±10.36 years. The mean expanded disability status scale (EDSS) score was 2.90±1.88, and mean annualized attack rate (ARR) was .65±.55. Of the 219 patients, 75.1% continued the immunomodulatory treatment. Thirty-three patients in the RRMS group and 23 patients in the SPMS group abandoned the immunomodulatory treatment. Treatment adherences were similar between patients with RRMS and SPMS (53%). Adherence revealed no correlation with age, ARR, PASAT score, and disease duration. However, higher EDSS and depression scores had significant positive correlation with adherence. Moreover, treatment adherence was noted to be lower in the group with higher education levels. Treatment discontinuation did not correlate with age, ARR, BDS, or PASAT scores. The disease duration and EDSS scores were found to be significantly correlated with treatment discontinuation. In this extensively followed up patients' group with multiple sclerosis, the ones with extended disease duration, higher disability, and more educated had higher rates of treatment discontinuation and lower levels of treatment adherence. The patient-reported outcomes and well-documented treatment adherence data will contribute to the neurologists' understanding of the patients' inclinations regarding the injectable treatments and help in better management of the immunomodulatory treatments.


Isolated renal mucormycosis masquerading as emphysematous pyelonephritis.
Mucormycosis is an acute, life-threatening infection and isolated renal involvement is rare. Due to the angioinvasive nature of the disease, it is rapidly progressive and can be lethal if not managed expeditiously. In patients with underlying conditions of immunosuppression, diabetes mellitus, transplantation, COVID-19, intravenous drug and substance use and pyelonephritis, which is unable to be controlled via regular antibiotics, mucormycosis must be considered on the differential and antifungals must be empirically started. Most cases are often diagnosed on histopathology, which causes delayed treatment and resolution. We present a case of emphysematous pyelonephritis diagnosed on imaging and was later found to have mucormycosis on histopathological examination.


CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion.
The functional significance of the chemokine receptor CCR5 in human breast cancer epithelial cells is poorly understood. Here, we report that CCR5 expression in human breast cancer correlates with poor outcome. CCR5+ breast cancer epithelial cells formed mammospheres and initiated tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5-negative breast cancer cells promoted tumor metastases and induced DNA repair gene expression and activity. CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing mediated by DNA-damaging chemotherapeutic agents. Single-cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is reexpressed selectively on cancerous, but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DNA damage response-based treatments, allowing a dose reduction of standard chemotherapy and radiation.Significance: This study offers a preclinical rationale to reposition CCR5 inhibitors to improve the treatment of breast cancer, based on their ability to enhance the tumor-specific activities of DNA-damaging chemotherapies administered in that disease. Cancer Res; 78(7); 1657-71. ©2018 AACR.


Microsimulation model of CT versus MRI surveillance of Bosniak IIF renal cystic lesions: should effects of radiation exposure affect selection of imaging strategy?
The objective of this study was to quantify the effects of radiation-induced cancer risks in patients with Bosniak category IIF lesions undergoing CT versus MRI surveillance. We developed a Markov-Monte Carlo model to determine life expectancy losses attributable to radiation-induced cancers in hypothetical patients undergoing CT versus MRI surveillance of Bosniak IIF lesions. Our model tracked hypothetical patients as they underwent imaging surveillance for up to 5 years, accounting for potential lesion progression and treatment. Estimates of radiation-induced cancer mortality were generated using a published organ-specific radiation-risk model based on Biological Effects of Ionizing Radiation VII methods. The model also incorporated surgical mortality and renal cancer-specific mortality. Our primary outcome was life expectancy loss attributable to radiation-induced cancers. A sensitivity analysis was performed to assess the stability of the results with variability in key parameters. The mean number of examinations per patient was 6.3. In the base case, assuming 13 mSv per multiphase CT examination, 64-year-old men experienced an average life expectancy decrease of 5.5 days attributable to radiation-induced cancers from CT; 64-year-old women experienced a corresponding life expectancy loss of 6.9 days. The results were most sensitive to patient age: Life expectancy loss attributable to radiation-induced cancers increased to 21.6 days in 20-year-old women and 20.0 days in 20-year-old men. Varied assumptions of each modality's (CT vs MRI) depiction of lesion complexity also impacted life expectancy losses. Microsimulation modeling shows that radiation-induced cancer risks from CT surveillance for Bosniak IIF lesions minimally affect life expectancy. However, as progressively younger patients are considered, increasing radiation risks merit stronger consideration of MRI surveillance.


Experimental, analytical, and computational investigation of mesh grid thermal physics in an electron gun with dispenser cathode.
Gridded electron guns are key components of various electron beam based vacuum tubes. Mesh grids may be utilized for electron beam extraction and control. As part of the electron beam may be intercepted by the mesh grid, heating occurs, which could translate into performance degradation of the vacuum tube or even failure. This paper introduces an analytical model based on first physics principles for mesh grid heating in an electron gun, toward generating the upper bound for the intercepted electron beam power. 3D simulations and exploratory experiments for mesh grid heating in an electron gun directionally confirm the predictions of the analytical model. This analytical approach may be leveraged further when the upper bounds of mesh grid heating in electron guns are needed, as well as for adjusting mesh grid topology to increase its robustness against electron beam heating.


Comparison of nimesulide and flurbiprofen in the treatment of non-infectious acute inflammation of the upper respiratory tract.
Sixty patients were enrolled in a controlled randomized single-blind study to compare the efficacy and tolerability of 200 mg/day nimesulide and 300 mg/day flurbiprofen given for 7 days, in the treatment of non-infectious acute inflammation of the upper respiratory tract. Patients were diagnosed as follows: pharyngitis, 20 (33.4%) cases; laryngitis 11 (18.3%) cases; tonsillitis, eight (13.3%) cases; and mixed forms, 21 (35.0%) cases. Both drugs showed the same efficacy in reducing mucosal congestion, local redness, fever and sore throat. Nimesulide treatment gave rise to fewer and less severe side-effects than flurbiprofen treatment.


Influence of aortic regurgitation after TAVI on left ventricular filling pattern.
Paravalvular aortic regurgitation after transcatheter aortic valve implantation is associated with a hemodynamic deterioration and a poor outcome. We aim to determine the early hemodynamic effect of paravalvular aortic regurgitation in relation with the change in the left ventricle filling pattern and to assess their clinical outcome. Eighty-two consecutive patients referred for transcatheter aortic valve implantation were included. Patients were classified according to the change in the left ventricular filling pattern, and significant paravalvular aortic regurgitation (grade ≥ 2) was reported. Follow-up and incidence of death and hospitalization for heart failure were reported. Sixteen patients (19·5%) presented a worsening of left ventricular filling pattern. The incidence of significant paravalvular aortic regurgitation was higher in the group with a worsening of left ventricular filling pattern (56·3% vs. 19·7%; P = 0·009). In the multivariate analysis, the only variable significantly associated with the worsening of left ventricular filling pattern was the significant paravalvular aortic regurgitation (OR 4·84; 95% CI 1·23 - 19·1; P = 0·024). During the follow-up (642·5 days), there was a higher incidence of the endpoint of death or hospitalization for heart failure in the group with a worsening of left ventricular filling pattern (62·5% vs. 31·8%; P = 0·042) and a lower event-free survival rate (long rank test = 0·013). The presence of a significant paravalvular aortic regurgitation is associated with a worsening in parameters of diastolic function. This finding should alert the cardiologist as patients with a worsening of left ventricular filling pattern present a higher incidence of paravalvular aortic regurgitation and a less favourable outcome.


[Study on the mechanism of Bushen Culuan Chongji treating "kidney deficiency and blood stasis" in ovulatory dysfunctional infertility].
Kidney deficiency and blood stasis is the main cause of ovulatory dysfunctional infertility. Kidney deficiency is the main pathological mechanism. Blood stasis is the main pathological manifestation, and it is an important factor throughout. Bushen Culuan Chongji is under the guidance of traditional Chinese medicine(TCM) theory, previous years of clinical experience, combined with the etiology and pathogenesis of anovulatory infertility and modern pharmacological research results, selected, not only maintains the TCM syndrome differentiation and different diseases features, but also reflects the superiority of the combination of disease. In the study of Bushen Culuan Chongji in the treatment of anovulatory infertility, there was no acute toxicity and no LD50 was detected. No adverse effects and side effects were found in the reproductive, genetic, toxicity, teratogenic, and perinatal tests in their high and low dose groups. In pharmacodynamics experiments, it can promote the development and maturation of follicles and the formation of corpus luteum in rats. Taking the kidney deficiency and blood stasis syndrome as the breakthrough point, systematically study the efficacy, safety and mechanism of six ovulatory dysfunctional infertility diseases, including abnormal uterine bleeding-ovulatory disorders, polycystic ovary syndrome, high prolactin, luteinized unruptured follicle syndrome, luteal phase defect and diminished ovarian reserve/premature ovarian failure. It verified the contribution degree of reinforcing kidney and resolving stasis TCM, reflected the characteristics of combination between disease differentiation and syndrome differentiation, interpreted the treatment principles of treating different diseases with the same method, and provided scientific basis for clinical treatment.


Optimization and application of the head space liver S9 equilibration technique for metabolic studies of organic solvents.
A head space liver S9 vial equilibration technique for qualitative and quantitative metabolism of volatile organic solvents in vitro is described and investigated for optimal experimental conditions with toluene and n-hexane as model substrates. The method was also used for studying the metabolic interaction between acetone and styrene. NADP+ was a critical cofactor in the system as concentrations above 2.5 mM resulted in inhibition of metabolism. Induction of cytochrome P450 by phenobarbital did not alter the observed cofactor dependency, and addition of vehicles such as rat blood did not enhance metabolism. Acetone-induced liver S9 increased the primary oxidation of styrene and also the formation of styrene oxide, but not significantly that of mandelic acid. Acetone as such had no effect on the metabolic elimination of styrene, indicating that the interaction is mainly on the level of enzyme induction occurring after long-term exposure to acetone. As earlier reports on styrene metabolism in vivo has not been able to detect styrene oxide in toxicokinetic studies with a sufficient degree of accuracy, the head space liver S9 vial equilibration technique may offer a fast and sensitive tool for screening of metabolic interactions between organic solvents when optimized for metabolic activity.


Immunomodulatory effect of diethylcarbamazine citrate plus filarial excretory-secretory product on rat hepatocarcinogenesis.
Diethylcarbamazine citrate (DEC) had a significance in anti-filarial chemotherapy, while excretory-secretory product (ES) is released from adult filarial females. The target of the current study was to examine the immunomodulatory effect of DEC, Setaria equina ES or a combination of them on rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN). In vitro effect of combined DEC and ES or ES alone on lipopolysaccharide (LPS)-stimulated rat peripheral blood mononuclear cells (PBMCs) was tested through IFN-γ assay in culture supernatants. In addition, single or repeated doses of DEC, ES or DEC+ES have been applied in white albino rats to test the effect on HCC. Levels of IFN-γ and anti-ES IgG antibodies in rat serum were assayed using ELISA. Hemolytic complement activity (CH50) was determined in serum while the concentration of nitric oxide (NO) was assayed in liver tissue. The infiltration of NK cells as well as the expression of MHC Iproliferating cell nuclear antigen (PCNA), inducible NO synthase (iNOS), Bcl2 and p53 were determined using immunohistochemistry. There was a dose-dependent increase in IFN-γ after in vitro exposure to DEC+ES. Repeated ES doses increased NO concentration (p<0.05) and expression of iNOS but reduced CH50 (p<0.001), while repeated DEC+ES doses could increase anti-ES IgG (p<0.01), IFN-γ level (p<0.05) and NK cell infiltration. The same treatments could also reduce the expression of MHC I expression, PCNA, Bcl2 and p53. This study has shown immunomodulatory and protective effects of DEC+ES repeated doses on rat HCC.


Metagenomic survey reveals global distribution and evolution of microbial sialic acid catabolism.
Sialic acids comprise a varied group of nine-carbon amino sugars found mostly in humans and other higher metazoans, playing major roles in cell interactions with external environments as well as other cells. Microbial sialic acid catabolism (SAC) has long been considered a virulence determinant, and appears to be mainly the purview of pathogenic and commensal bacterial species associated with eukaryotic hosts. Here, we used 2,521 (pre-)assembled metagenomes to evaluate the distribution of SAC in microbial communities from diverse ecosystems and human body parts. Our results demonstrated that microorganisms possessing SAC globally existed in non-host associated environments, although much less frequently than in mammal hosts. We also showed that the ecological significance and taxonomic diversity of microbial SAC have so far been largely underestimated. Phylogenetic analysis revealed a strong signal of horizontal gene transfer among distinct taxa and habitats, and also suggested a specific ecological pressure and a relatively independent evolution history in environmental communities. Our study expanded the known diversity of microbial SAC, and has provided the backbone for further studies on its ecological roles and potential pathogenesis.


Activity of Alcohol Dehydrogenase and Aldehyde Dehydrogenase in Lung Cancer Cells.
The aim of this study was to define the alterations in the activity of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in normal and cancerous lung cells. Lung tissues were taken from 36 patients during surgical resection of cancer. The activities of tested enzymes were measured by spectrofluorometric method (ADH I, ADH II, total ALDH) and photometric method (ADH III, ADH IV, total ADH). The activities of class II and III ADH were significantly lower in lung cancer cells compared to histologically normal lung tissue. Reduced activity of isoenzyme class II ADH may affect disorders in retinoic acid biosynthesis, leading to its deficit. Lower ADH III activity may result in depletion of glutathione, and in initiation of oxidative stress, leading to cancer progression. These data suggest that alterations in ADH isoenzyme activities can contribute to carcinogenesis in human lungs.


A mechanistic model of small intestinal starch digestion and glucose uptake in the cow.
The high contribution of postruminal starch digestion (up to 50%) to total-tract starch digestion on energy-dense, starch-rich diets demands that limitations to small intestinal starch digestion be identified. A mechanistic model of the small intestine was described and evaluated with regard to its ability to simulate observations from abomasal carbohydrate infusions in the dairy cow. The 7 state variables represent starch, oligosaccharide, glucose, and pancreatic amylase in the intestinal lumen, oligosaccharide and glucose in the unstirred water layer at the intestinal wall, and intracellular glucose of the enterocyte. Enzymatic hydrolysis of starch was modeled as a 2-stage process involving the activity of pancreatic amylase in the lumen and of oligosaccharidase at the brush border of the enterocyte confined within the unstirred water layer. The Na+-dependent glucose transport into the enterocyte was represented along with a facilitative glucose transporter 2 transport system on the basolateral membrane. The small intestine is subdivided into 3 main sections, representing the duodenum, jejunum, and ileum for parameterization. Further subsections are defined between which continual digesta flow is represented. The model predicted nonstructural carbohydrate disappearance in the small intestine for cattle unadapted to duodenal infusion with a coefficient of determination of 0.92 and a root mean square prediction error of 25.4%. Simulation of glucose disappearance for mature Holstein heifers adapted to various levels of duodenal glucose infusion yielded a coefficient of determination of 0.81 and a root mean square prediction error of 38.6%. Analysis of model behavior identified limitations to the efficiency of small intestinal starch digestion with high levels of duodenal starch flow. Limitations to individual processes, particularly starch digestion in the proximal section of the intestine, can create asynchrony between starch hydrolysis and glucose uptake capacity.


[Role of therapeutics for allergic diseases in targeting histamine H1 receptor gene expression].
Histamine H(1) receptors are down-regulated as one step in receptor desensitization. Five phosphorylation sites of the H(1) receptor seem to play a key role in receptor down-regulation. In contrast, an increase in the H(1) receptor expression level following its mRNA elevation was found in the nasal mucosa in hypersensitivity model rats. Up-regulation of the H(1) receptor was induced by the direct stimulation of the H(1) receptor. H(1) receptor up-regulation was suppressed by pretreatment with antiallergic agents.


[Pectus excavatumn and carinatum in children and adolescents : what to say, what to do ?]
In children presenting with a pectus excavatum (PE) or pectus carinatum (PC) an underlying syndrome including Marfan's syndrome needs to be excluded. In adolescents, severe chest wall deformities may cause cardiac or respiratory problems but most commonly they have a psychological impact. The conservative treatment is a Vacuum Bell for PE, and a Dynamic Compression System for PC ; they play an increasing role in young patients. These devices need to be worn multiple hours per day for several months for an optimal result. Surgery is usually reserved for adolescents. The Nuss procedure for PE, also known as minimal invasive repair of PE offers excellent results. Sterno-chondro-plasty with stabilisation of the sternum with struts clipped to the ribs offers the same good results for PC. In our opinion, a multidisciplinary approach is preferable.


The Relationship between APOL1 Structure and Function: Clinical Implications.
Common variants in the APOL1 gene are associated with an increased risk of nondiabetic kidney disease in individuals of African ancestry. Mechanisms by which APOL1 variants mediate kidney disease pathogenesis are not well understood. Amino acid changes resulting from the kidney disease-associated APOL1 variants alter the three-dimensional structure and conformational dynamics of the C-terminal α-helical domain of the protein, which can rationalize the functional consequences. Understanding the three-dimensional structure of the protein, with and without the risk variants, can provide insights into the pathogenesis of kidney diseases mediated by APOL1 variants.


Basal cell carcinoma incompletely excised: a case-control study on recurrence.
There are no univocal opinions on the management of incompletely excised basal cell carcinoma (BCC); early re-excision or clinical observation represent the two possible options. The main objective of the present study was to compare the rate of recurrence between incompletely excised BCCs, not re-excised, and completely excised BCCs within a 3-5 year follow-up period in order to reach indications about the most appropriate care strategy. We conducted a case-control study on a cohort of 39 incompletely excised and 107 completely excised BCCs. Patients were recalled for a visit. Three (8%) BCCs recurred among the incompletely excised tumors and 3 (3%) among those completely excised, without significant difference. Advanced age and chronic occupational sun exposure were found to be associated with BCC recurrence. Thirty-seven percent of patients developed new BCCs during follow-up. Half of the patients did not adhere to the scheduled visits after BCC excision. The rate of patients with diagnosis of new or recurrent BCC at the recall visit was higher among non-adherent patients. In the case of incompletely excised BCCs, long-term clinical observation may be pursued, especially when immediate surgical re-excision is contraindicated. Difficulty in maintaining follow-up due to poor patient adherence represents a concern in clinical practice.


A dynamic deterministic model to optimize a multiple-trait selection scheme.
A mathematical approach was developed to model and optimize simultaneous selection on 2 traits, a quantitative trait with underlying polygenic variation and a monogenic trait (e.g., resistance to a disease). A deterministic model allows global optimization of the selection scheme to maximize the frequency of the desired genotype for the monogenic trait, while minimizing the loss of genetic progress on the polygenic trait. An additive QTL or gene was considered. Breeding programs with overlapping generations, different selection strategies for males and females, and assortative mating were modeled. A genetic algorithm was used to solve this optimization problem. This modeling approach may easily be adapted to a variety of underlying genetic models and selection schemes. This model was applied to an example where selection on the Prp gene for scrapie resistance was introduced as an additional selection criterion in an already existing dairy sheep selection scheme.


Metabolism and biological potency of retro-retinyl acetate in the rat.
1. retro-Retinyl acetate was shown to exert its biological activity by conversion into vitamin A. 2. When administered orally, retro-retinyl acetate was hydrolysed to retro-retinol in the intestine, isomerized to retinol and esterified before being transported to the liver for storage. 3. Administration of the compound at as high a dose as 4.0mg./day for 4 days led to the accumulation of both vitamin A and retro-vitamin A in the liver. The amount of retro-vitamin A in liver gradually decreased until it was almost completely converted into vitamin A in 18 days. 4. Intraperitoneal administration of the compound led to the accumulation of both vitamin A and retro-vitamin A in liver and other tissues. No vitamin A was detected in any tissue of rats receiving retro-retinyl acetate intraperitoneally after enterectomy. 5. The small intestine is the major site of conversion of retro-vitamin A into vitamin A. The conversion could also be demonstrated by everted intestinal sacs. 6. The biological potency of retro-retinyl acetate determined by the rat-growth assay was 20.5% that of all-trans-retinyl acetate, when given orally.


Meeting The Health of the Nation target for skin cancer: problems with tackling prevention and monitoring trends.
The White Paper The health of the nation challenges us to halt the rising incidence and mortality from skin cancer. Means of achieving this include various approaches to educating the public and modifying sun exposure and promotion of early detection of cancers. Some initiatives can be organized locally but others require national coordination. Evaluation of the impact on health and the cost of preventive programmes is important because the effectiveness of health education packages and campaigns that aim to reduce the incidence or death from skin cancer has yet to be proved. As the majority of skin cancers do not metastasize, it is on melanoma that efforts to improve registration should be focused. Cancer registries have particular difficulty in monitoring the incidence of skin cancer where treatment is simply excision. Improved ascertainment and a shift towards early diagnosis will cause artefactual increases in incidence. Investigation of the trends will therefore require careful interpretation.


A comparative study of dithranol cream, 0.25% and 0.1%, and dithranol ointment 0.25% in the treatment of psoriasis.
A trial was carried out in 60 patients with relatively stable psoriasis to compare the effectiveness, tolerance and cosmetic properties of dithranol in a cream base (0.1% and 0.25%) or in the form of a soft paraffin ointment (0.25%). Patients were assigned at random to receive treatment with one or other of the three formulations, applied once daily, over a period of 4 weeks. Assessments were made initially and after 2 and 4 weeks of induration, redness, scaling and pruritus and during the trial of staining of clothes and linen, skin discolouration and burning. There was no significant difference in effect between dithranol cream 0.25% and dithranol ointment 0.25%, while both showed a better effect than dithranol cream 0.1% (p less than 0.05). The dithranol cream preparations were significantly better (p less than 0.05) than dithranol ointment 0.25% regarding all the cosmetic variables after 2 as well as after 4-weeks' treatment. The same applied to the patients' overall evaluation of the cosmetic acceptability. Three patients in the dithranol ointment group were considered as treatment failures. One of them refused to continue with the treatment due to burning and another due to burning and staining.


Changes in Emergency Department Volumes at the Largest U.S. Military Hospital During the COVID-19 Pandemic.
The coronavirus-2019 (COVID-19) pandemic has significantly impacted global healthcare delivery. Brooke Army Medical Center (BAMC) is the DoD's largest hospital and a critical platform for maintaining a ready medical force. We compare temporal trends in patient volumes and characteristics in the BAMC emergency department (ED) before versus during the pandemic. We abstracted data on patient visits from the BAMC ED electronic medical record system. Data included patient demographics, visit dates, emergency severity index triage level, and disposition. We visually compared the data from January 1, 2019 to November 30, 2019 versus January 1, 2020 to November 30, 2020 to assess the period with the most apparent differences. We then used descriptive statistics to characterize the pre-pandemic control period (1 March-November 30, 2019) versus the pandemic period (1 March-November 30, 2020). Overall, when comparing the pre-pandemic and pandemic periods, the median number of visits per day was 232 (Interquartile Range (IQR) 214-250, range 145-293) versus 165 (144-193, range 89-308, P < .0001). Specific to pediatric visits, we found the median number of visits per day was 39 (IQR 33-46, range 15-72) versus 18 (IQR 14-22, range 5-61, P < .001). When comparing the median number of visits by month, the volumes were lower during the pandemic for all months, all of which were strongly significant (P < .001 for all). The BAMC ED experienced a significant decrease in patient volume during the COVID-19 pandemic starting in March 2020. This may have significant implications for the capacity of this facility to maintain a medically ready force.


Deciphering the Metabolome under Stress: Insights from Rodent Models.
Despite intensive research efforts to understand the molecular underpinnings of psychological stress and stress responses, the underlying molecular mechanisms remain largely elusive. Towards this direction, a plethora of stress rodent models have been established to investigate the effects of exposure to different stressors. To decipher affected molecular pathways in a holistic manner in these models, metabolomics approaches addressing altered, small molecule signatures upon stress exposure in a high-throughput, quantitative manner provide insightful information on stress-induced systemic changes in the brain. In this review, we discuss stress models in mice and rats, followed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolomics studies. We particularly focus on acute, chronic and early life stress paradigms, highlight how stress is assessed at the behavioral and molecular levels and focus on metabolomic outcomes in the brain and peripheral material such as plasma and serum. We then comment on common metabolomics patterns across different stress models and underline the need for unbiased -omics methodologies and follow-up studies of metabolomics outcomes to disentangle the complex pathobiology of stress and pertinent psychopathologies.


Morphological, olfactory, and vocal development in big brown bats.
Using a within subjects design, we documented morphological, bioacoustical and behavioral developmental changes in big brown bats. Eptesicus fuscus pups are born naked and blind but assume an adult-like appearance by post-natal day (PND) 45 and flight by PND 30. Adult females use spatial memory, acoustic and olfactory cues to reunite with offspring, but it is unclear if pups can recognize maternal scents. We tested the olfactory discrimination abilities of young E. fuscus pups and found they exhibited no odor preferences. Pups also emit distinct vocalizations called isolation calls (i-calls) that facilitate mother-offspring reunions, but how pups shift their vocalizations from i-calls to downward frequency modulated (FM) sweeps used in echolocation remains unclear. Between PND 0-9, pups emitted mainly long duration, tonal i-calls rich in harmonics, but after they switched to short duration, downward FM sweeps with fewer harmonics. Call maximum frequency and repetition rate showed minor changes across development. Signal duration, bandwidth, and number of harmonics decreased, whereas the maximum, minimum and bandwidth of the fundamental, and peak spectral frequency all increased. We recorded vocalizations during prolonged maternal separation and found that isolated pups called longer and at a faster rate, presumably to signal for maternal assistance. To assess how PND 13 pups alter their signals during interactions with humans we compared spontaneous and provoked vocalizations and found that provoked calls were spectrally and temporally more similar to those of younger bats suggesting that pups in distress emit signals that sound like younger bats to promote maternal assistance.


Understanding cystic-fibrosis-related diabetes: best thought of as insulin deficiency?
The limited available evidence supports the use of insulin treatment in CFRD. This fits with the dominant problem in CFRD being insulin deficiency and progressive beta cell dysfunction, making tablets that stimulate the beta cell unlikely to be a successful strategy. It is possible that patients with IGT or CFRD with moderate hyperglycaemia (e.g. relative preservation of fasting glucose) may initially respond to beta cell secretagogues. A large randomized prospective trial in the USA should answer this point in the next few years.


Correlation between crystal structure and mobility in organic field-effect transistors based on single crystals of tetrathiafulvalene derivatives.
Recently, it was reported that crystals of the organic material dithiophene-tetrathiafulvalene (DT-TTF) have a high field-effect charge carrier mobility of 1.4 cm(2)/(V x s). These crystals were formed by a simple drop-casting method, making this material interesting to investigate for possible applications in low-cost electronics. Here, organic single-crystal field-effect transistors based on materials related to DT-TTF are presented and a clear correlation between the crystal structure and the electrical characteristics is observed. The observed relationship between the mobilities in the different crystal structures is strongly corroborated by calculations of both the molecular reorganization energies and the maximum intermolecular transfer integrals. The most suitable materials described here exhibit mobilities that are among the highest reported for organic field-effect transistors and that are the highest reported for solution-processed materials.


Differences in sympathoadrenal, hormonal, and metabolic adaptation to submaximal and maximal arm and leg work compared with whole stroke in breast-style swimming.
During work on land adaptational reactions of circulation and hormones are influenced by the body position, the activated muscle mass, and the working extremities. The aim of this study was to explore the additional effect of water immersion during swimming on cardiocirculatory, metabolic, and hormonal regulation under different working conditions. Twelve young men not specifically trained in swimming underwent swimming tests on 3 different days. They had to swim breast stroke in total as well as isolated with legs or arms only each for 10 min at submaximal intensity and 150 m or 100 m at maximal intensity. This study was focused on changes of catecholamines (CA), heart rate (HR), blood pressure (BP), glucose, lactate, plasma renin activity (PRA), and plasma aldosterone (PA). Additionally, parameters of the electrolyte-volume homeostasis were investigated. Norepinephrine (NE) and epinephrine (EPI) increased during swimming under submaximal and maximal conditions. The augmentation of CA and HR was the highest after swimming whole stroke and the lowest after swimming arm stroke only. They were related to intensity within one type of swimming and showed a dependence on muscle mass independent from lactate or glucose levels when the different types of swimming were compared, although a positive correlation between CA and lactate levels was found. The BP was higher after leg work than after arm work, contrary to observations done on land regarding the comparable submaximal work loads. We suppose that this is an effect of water immersion and the horizontal body position whereby the central hemodynamic circulation becomes stabilized.(ABSTRACT TRUNCATED AT 250 WORDS)


Microbial population response to changes of the operating conditions in a dynamic nutrient-removal sequencing batch reactor.
A nutrient-removal sequencing batch reactor operated with short anaerobic/aerobic cycles was subjected to different operating conditions, namely, cycle length, feeding pattern and feed composition. The changes in microbial population, as well as the contribution of microbial groups to the total nutrient removal, were estimated using the kinetic parameters obtained in this study. Denitrifying polyphosphate-accumulating organisms (DPAOs) were detected in the system, representing a fraction of 23% of phosphorus-accumulating organisms (PAOs). The results suggest that DPAOs and non-DPAOs are different microorganisms. The presence of nitrate in the feed stimulated DPAOs to predominate over non-DPAOs. Feeding the reactor with a mixture of organic substrates also stimulated DPAOs. Glycogen-accumulating organisms (GAOs) were likely to be present in the system and their development over PAOs was apparently favoured by increasing the aeration time and feeding during the aerobic phase. In contrast, the presence of propanoate in the feed apparently favoured PAOs over GAOs.


Radionuclide scanning of the spleen. Technical modification, normal variants and dimensions.
In order to cut down the time needed for the preparation of the thermally damaged erythrocytes, the effect of heat was combined with the use of a higher concentration of ACD. Heating of the 51Cr tagged red cells was performed in a water bath, at 50 degrees C for 15 minutes, in the presence of ACD in the ratio of one ml ACD for every 3 ml blood. Using this technique, the obtained splenic scans in 20 normal individuals were excellent in quality. In the posterior view, the spleen was oval with an oblique long axis in 65% of the cases and transverse long axis in another 15%. In the remaining 20% the spleen was globular. The average measurements of the spleen were 10.5 X 7,1 cm, with a circumference of 29.8 cm. By planimetry, the surface area of the spleen averaged (59 +/- 12.4) cm2 (Mean +/- 1 S.D.) In the lateral projection, the surface area of the splenic scan was larger by an average of 40% than the picture obtained through the posterior approach in all the six examined subjects.


Flexibility in starfish behavior by multi-layered mechanism of self-organization.
Understanding animal behavior as a product of natural selection sometimes result in an underestimation of the animal's adaptability: lower animals with poor mental capabilities are usually considered to simply exhibit innate behavioral patterns. Self-organized behavior may exhibit both stability of certain behavioral patterns and flexibility in adopting those patterns. Thus, the self-organization processes of starfish arm and tube feet movements are investigated, by observing obstacle avoidance behavior and tube feet of moving starfish. As starfish have no central nervous systems, their behaviors are the result of certain self-organization processes. Starfish have hierarchically constructed motor organs consisting of arms and tube feet. The collective behavior of the tube feet does not function only as simple fluctuations in the arms' coordination. As a result, starfish seem to exhibit more versatile behavioral changes than expected from the original model of a self-organized behavior.