Ossification of the ligamentum flavum in the thoracic spine mimicking sciatica in a young baseball pitcher:a case report.
Thoracic ossification of the ligamentum flavum (OLF) is a pathological condition that causes myelopathy, with unilateral lower extremity pain rarely a feature in the presenting complaint. Moreover, most symptomatic cases of thoracic OLF occur in middle-aged men, with younger individuals rarely affected. We present a rare case of severe and chronic unilateral buttock and leg pain mimicking sciatica due to thoracic OLF in a professional baseball pitcher. A 28-year-old, right-handed, Japanese professional baseball pitcher experienced intractable left leg pain with numbness and spasticity. After the initial presentation, extensive testing focusing on lumbar, hip, and pelvis lesions failed to identify a cause for the pain. One year after onset, careful neurological examination showed signs of upper motor neuron disturbance, and thoracic computed tomography and magnetic resonance imaging revealed thoracic OLF at the level of the thoracolumbar junction. After resection of the thoracic OLF, the pain, numbness, and spasticity completely resolved. He resumed full training and was pitching in top condition within four months after surgery. Though rare, thoracic OLF should be considered in the differential diagnosis of lower extremity pain in young athletes, especially amongst high-level baseball pitchers.


Knowledge regarding cancer-related fatigue: a survey of physical therapists and individuals diagnosed with cancer.
Cancer-related fatigue (CRF) is a common side effect and remains under-diagnosed. Screening of CRF by physical therapists (PTs) and patient perspectives of their experiences has not been comprehensively examined. To survey PTs to understand the frequency of CRF screening, and to assess the knowledge and experiences of survivors as it relates to CRF. Two separate electronic surveys developed by the authors were distributed. One targeted oncology PTs, the other for adult survivors of cancer. Of the 199 PT respondents, 36% reported screening for CRF at every encounter. Screening included interviews (46%) and/or standardized questionnaires (37%). The most common barriers to receiving treatment for CRF was lack of physician referrals and time constraints. Of patient responses (n = 61), 84% reported CRF as an important ongoing issue; 77% reported that they initiated the discussion about CRF with their provider, and 23% reported being told there were treatment options for CRF. CRF is common among cancer survivors. However, consistent screening by PTs is lacking. Patients with CRF frequently initiated the conversation with their providers because of symptoms and many patients were not told of treatment options. These findings represent a substantial gap in clinical practice regarding CRF screening and management.


The risk of developing breast cancer in relation to mammography findings.
Several studies have shown that it is possible to use the parenchymal patterns disclosed by mammography to differentiate various groups with a high risk of developing breast cancer. Accordingly, a patient series of 597 women who had undergone mammography during the period 1971-1975 was examined and classified according to Wolfe's system. A follow-up of 513 patients five to nine years after the mammography revealed no statistical difference in the tendency to develop breast cancer using Wolfe's parenchymal pattern method. The study shows that those in the group with pronounced fibroadenomatous changes, which were primarily studies radiologically, have an incidence of breast cancer three times as high as that found in the population as a whole.


The Toxic Effects of Tetrachlorobisphenol A in Saccharomyces cerevisiae Cells via Metabolic Interference.
Tetrachlorobisphenol A (TCBPA) is a common flame retardant detected in different environments. However, its toxic effects on animals and humans are not fully understood. Here, the differential intracellular metabolites and associated gene expression were used to clarify the metabolic interference of TCBPA in Saccharomyces cerevisiae, a simple eukaryotic model organism. The results indicated that TCBPA treatment promoted the glycolysis pathway but inhibited the tricarboxylic acid (TCA) cycle, energy metabolism and the hexose monophosphate pathway (HMP) pathway. Thus, the HMP pathway produced less reducing power, leading to the accumulation of reactive oxygen species (ROS) and aggravation of oxidative damage. Accordingly, the carbon flux was channelled into the accumulation of fatty acids, amino acids and glycerol instead of biomass production and energy metabolism. The accumulation of these metabolites might serve a protective function against TCBPA stress by maintaining the cell membrane integrity or providing a stable intracellular environment in S. cerevisiae. These results enhance our knowledge of the toxic effects of TCBPA on S. cerevisiae via metabolic interference and pave the way for clarification of the mechanisms underlying TCBPA toxicity in animals and humans.


Regulation of hepatic cholesterol metabolism in CETP/LDLr mice by cholesterol feeding and by drugs (cholestyramine and lovastatin) that lower plasma cholesterol.
1. The hepatic mechanisms involved in the simultaneous regulation of plasma cholesterol concentration and cholesteryl ester transfer protein (CETP) activity were investigated by sharply modifying the hepatic rates of cholesterol synthesis. This was accomplished by cholestyramine, lovastatin and cholesterol feeding in human CETP transgenic mice cross-bred with low-density lipoprotein receptor (LDLr)-knockout mice, generating CETP(+/-)/LDLr(+/-) mice, which present a plasma lipoprotein profile resembling that of humans. 2. Analyses of pooled data showed that the plasma CETP activity correlated positively with plasma total cholesterol concentration, hepatic CETP mRNA and the liver microsomal cholesterol content; a negative correlation was found between plasma CETP activity and the liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and LDLr mRNA levels. These coordinated events represent an efficient control system that stabilizes the cell cholesterol content. 3. Nonetheless, not all cholesterol metabolism regulatory systems seem to fit into a coherent pattern of responses, suggesting that other unknown cellular mechanisms play roles depending on the type of pharmacological intervention. 4. For example, microsomal cholesterol content was not affected by cholestyramine, but was increased on cholesterol feeding (as predicted), and, surprisingly, on lovastatin treatment. Furthermore, although both plasma cholesterol-lowering drugs increased CYP7A1 mRNA and had no effect on CYP27 mRNA, other metabolic components were differentially modified. Cholestyramine and lovastatin, respectively, did not modify and increased both HMG-CoA and sterol responsive element binding protein 1c mRNA, did not modify and lowered liver X receptor alpha mRNA, lowered and increased ATP binding cassette A1 mRNA and lowered and did not modify scavenger receptor B1 mRNA. 5. That is, different to unabsorbed cholestyramine, lovastatin, as an absorbed plasma cholesterol-lowering drug, may have modified the activity of other unknown genes that play roles in the interaction of CETP with the metabolism of hepatic cholesterol.


Adult human sarcomas. I. Basic science.
When connective tissue undergoes malignant transformation, glioblastomas and sarcomas arise. However, the ancient biochemical mechanisms, which are now operational in sarcomas distorted by mutations and gene fusions in misaligned chromosomes, were originally acquired by those cells that emerged during the Cambrian explosion. Preserved throughout evolution up to the genus Homo, these mechanisms dictate the apoptosis- and senescence-resistant immortality of malignant cells. A 'retroviral paradox' distinguishes human sarcomas from those of the animal world. In contrast to the retrovirally induced sarcomatous transformation of animal (avian, murine, feline and simian) cells, human sarcomas have so far failed to yield a causative retroviral isolate. However, the proto-oncogenes/oncogenes transduced from their host cells by retroviruses of animals are the same that are active in human sarcomas. Since the encoded oncoproteins arise after birth, they are recognized frequently by the immune system of the host. Immune lymphocytes that kill autologous sarcoma cells in vitro commonly fail to do so in vivo. Sarcoma vaccines generate immune T- and natural killer cell reactions; even when vaccinated patients do not show a clinical response, their tumors become more sensitive to chemotherapy. The aim of this review is to lay a solid molecular biological foundation for the conclusion that targeting the sarcoma oncogenes will result in regression of the disease.


Ox-inflammasome involvement in neuroinflammation.
Neuroinflammation plays a crucial role in the onset and the progression of several neuropathologies, from neurodegenerative disorders to migraine, from Rett syndrome to post-COVID 19 neurological manifestations. Inflammasomes are cytosolic multiprotein complexes of the innate immune system that fuel inflammation. They have been under study for the last twenty years and more recently their involvement in neuro-related conditions has been of great interest as possible therapeutic target. The role of oxidative stress in inflammasome activation has been described, however the exact way of action of specific endogenous and exogenous oxidants needs to be better clarified. In this review, we provide the current knowledge on the involvement of inflammasome in the main neuropathologies, emphasizing the importance to further clarify the role of oxidative stress in its activation including the role of mitochondria in inflammasome-induced neuroinflammation.


Investigations of anti-inflammatory activity of Jigrine.
Jigrine, a polypharmaceutical herbal formulation containing 14 medicinal plants is used in the Unani system of medicine for the treatment of liver ailments. The antiinflammatory activity of Jigrine (0.5 ml and 1.0 ml/kg, po), was evaluated against acute inflammation caused by carrageenin (injecting 0.1 ml of 1% carrageenin in 0.9% NaCl solution into plantar surface of the hind paw of the rat) and the effect of Jigrine (1 ml/kg/day, po for 7 days) was also studied on the sub-acute inflammation induced by cotton pellet granuloma. The paw volume, biochemical parameters like tissue AST, ALT, gamma-GTP and lipid peroxides and dry wt. of granuloma were measured to assess the anti-inflammatory activity. It showed a significant anti-inflammatory activity as evidenced by lowering the elevated levels of paw volume and biochemical parameters. But it could not reduce the sub-acute inflammation caused by cotton pellet granuloma. The study suggests that Jigrine has significant effect only on acute phase of inflammation caused by carrageenin. Antioxidant and membrane stabilizing action of Jigrine might be responsible for its anti-inflammatory effect.


1-[6-(6-Acetyl-pyridin-2-yl)pyridin-2-yl]ethanone.
In the title compound, C(14)H(12)N(2)O(2), the asymmetric unit comprises one half-mol-ecule with an inversion center between the pyridine rings. The rings are trans coplanar with the acetyl groups deviating slightly from the mean planes, making a dihedral angle of 4.63 (4)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, forming a supra-molecular sheet parallel to (100).


Influence of Staphylococcus epidermidis on Collagen Crimp Patterns of Soft Tissue Allograft.
Postoperative infections, commonly from Staphylococcus epidermidis, may result in anterior cruciate ligament graft failure and necessitate revision surgery. In biomechanical studies, S. epidermidis has been shown to establish biofilms on tendons and reduce graft strength. The goal of this study was to determine the effect of bacterial bioburden on the collagen structure of tendon. It was hypothesized that an increase in S. epidermidis biofilm would compromise tendon crimp, a pattern necessary for mechanical integrity, of soft tissue allografts. Controlled laboratory study. Cultures of S. epidermidis were used to inoculate tibialis anterior cadaveric tendons. Conditions assessed included 5 × 105 colony-forming units or concentrated spent media from culture (no living bacteria). Incubation times of 30 minutes, 3 hours, 6 hours, and 24 hours were utilized. Second-harmonic generation imaging allowed for visualization of collagen autofluorescence. Crimp lengths were determined using ImageJ and compared based on incubation time. Incubation time positively correlated with increasing S. epidermidis bioburden. Both fine and coarse crimp patterns lengthened with increasing incubation time. Significant coarse crimp changes were observed after only 30-minute incubations (P < .029), whereas significant fine crimp lengthening occurred after 6 hours (P < .0001). No changes in crimp length were identified after incubation in media lacking living bacteria. The results of this study demonstrate that exposure to S. epidermidis negatively affects collagen crimp structure. Structural alterations at the collagen fiber level occur within 30 minutes of exposure to media containing S. epidermidis. Our study highlights the need for antimicrobial precautions to prevent graft colonization and maximize graft mechanical strength.


Typhoon hazards in the Shanghai area.
There are three major typhoon hazards that apply to the Shanghai area. First, galeforce winds can damage buildings and service facilities. The most severe damage from this occurs only when a typhoon strikes Shanghai directly. Second, both the urban and rural sections of Shanghai are liable to flooding during typhoon seasons. These floods occur when typhoon-induced storm surges coincide with high spring tides and meet with high discharges from the river network as a result of the typhoon downpours. Third, typhoon-induced torrential rain has caused waterlog hazards, particularly in the most densely populated parts of Shanghai. The waterlog hazard has been exacerbated by land subsidence and poor management of pumping systems. In order to prevent disasters happening and reduce the scale of damage, the government has issued construction guidelines and invested in flood defences. Further measures are to be brought in including engineering projects, educational programmes and insurance policies.


Radiographic identification using midline medical sternotomy wires.
Forensic anthropologists are regularly asked to assist with the identification of unknown individuals using comparative medical radiography. This study addressed the use of midline medical sternotomy wires as a means for personal identification. Antemortem and postmortem radiographic comparisons were completed by 46 professional forensic anthropologists and anthropology graduate students familiar with comparative medical radiography as a technique for assessing identification. Participants were asked to make five radiographic matches from a pool of 20 radiographs. Participants also completed an anonymous survey detailing their education level and experience making radiographic comparisons. Participants were 99.5% accurate in matching the radiographs. Sensitivity was 98.7%, and specificity was 99.7%. Logistic regression analysis found no statistically significant differences in the participants' ability to make a correct match. As the high accuracy rates indicate, the shape, size, and various characteristics of the sternotomy wires are individualizing and can confidently be used when assisting with personal identification cases.


Physician Judgments and the Burden of Chronic Pain.
In a moderated mediation model, this study examined the interaction effect of pain severity and medical evidence on physician judgments of chronic pain. The effects of higher pain severity on physician judgments were expected to be mediated through anticipated clinical burden, but only when medical evidence was low. Participants were randomly assigned to one of six case descriptions of a chronic pain patient in a 3 × 2 design that varied by reported pain severity (4, 6, 8/10) and medical evidence (low vs high). An academic training program for medical residents/fellows. Residents/fellows in clinical departments at postgraduate year 2 or higher (N = 109). Participants read case descriptions and then made judgments about the patient and rated the level of burden they expected to assume in treating the patient. Higher pain severity occasioned greater pain discounting and higher likelihood of prescribing opioid medication. When medical evidence was low, participants had less trust in the patient's pain report, attributed pain more to psychosocial than medical factors, and were less likely to refer for possible surgery. Analyses yielded no support for moderated mediation as expected burden was high across all conditions. Significant associations were found between expected burden and multiple clinical judgments. Results did not support the proposed moderated mediation model as all patients were expected to be burdensome across clinical presentations, reflecting negative expectations of patients with chronic pain. Such expectations can have adverse implications for patient-provider communication, shared decision-making, and the delivery of personalized care.


Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine model of inflammatory arthritis.
To determine the nature of the initial changes of joint inflammation occurring before, at the time of, and shortly after onset of clinically apparent arthritis. Human tumor necrosis factor (TNF)-transgenic mice were assessed for clinical, histologic, immunophenotypic, serologic, and molecular changes at the preclinical phase of arthritis, at the onset of disease, and at the stage of early clinical disease. In addition, the effects of a genetic osteoclast deficiency and pharmacologic inhibition of TNF were studied in these initial phases of disease. Initial articular changes were observed even before the start of clinical symptoms. Infiltration of the tendon sheaths by granulocytes and macrophages as well as formation of osteoclasts next to the inflamed tendon sheaths were the first pathologic events. Tenosynovitis rapidly led to remodeling of the sheaths into pannus-like tissue, which formed osteoclasts that invaded the adjacent mineralized cartilage. Early lesions were associated with up-regulation of interleukin-1 (IL-1) and IL-6 as well as activation of p38 MAPK and ERK. In contrast, absence of osteoclasts led to uncoupling of tenosynovitis from invasion into cartilage and bone. TNF blockade also attenuated the pathologic changes associated with tenosynovitis. Structural damage begins even before the onset of clinical symptoms of arthritis and involves the tendon sheaths as well as adjacent cartilage and bone. These results suggest that tenosynovitis is an initiating feature of arthritis and that joint destruction starts right from the onset of disease. Our findings thus underscore the importance of immediate initiation of an effective therapy in patients with rheumatoid arthritis.


Construction of antisense Bmi-1 expression plasmid and its inhibitory effect on K562 cells proliferation.
Bmi-1 gene determines the proliferative capacity of normal and leukemia stem cells. Expression of Bmi-1 has been found in all types of myeloid leukemia cells in both humans and mice. This study aimed at assessing the effect of antisense Bmi-1 expression on K562 cells proliferation and p16 protein (p16) expression. A transcriptional repressor, Bmi-1 cDNA was cloned by reverse transcriptase polymerase chain reaction (RT-PCR) of its mRNA from K562 cells. A plasmid expressing antisense Bmi-1 mRNA was then constructed by reverse design of PCR primers and cloned to the plasmid pLNCX2; G418 was added to the medium after the plasmid was successfully introduced in K562 cells by lipofectin-mediated DNA transfection. The effects of the antisense expression on the proliferation of K562 cells were analyzed by using microculture tetrazolium and colony forming. Cell cycle was analyzed by using flow cytometry. The p16 expression of K562 cells was observed by immunofluorescence histochemical stain. K562 cells transfected with antisense Bmi-1 plasmid grew significantly slower than that of controls (the parental K562 and cells transfected with empty plasmid). The colony forming ability of antisense Bmi-1 plasmid transfected cells decreased significantly (P < 0.01) compared with controls. The p16 expression of cells transfected with antisense Bmi-1 was upgraded more apparently than that of controls. The antisense Bmi-1 gene can inhibit the growth of K562 cell and upgrade expression of p16 in K562 cells.


Evaluation of institutional readiness at sites within the UK NHS using a novel advanced therapy medicinal product assessment tool.
Aim: This paper reports on a study to assess institutional readiness (IR) of UK National Health Service sites that form part of the Northern Alliance Advanced Therapy Treatment Centre to deliver advanced therapy medicinal products (ATMPs). The paper discusses the development of an assessment tool to support self-assessment of IR in healthcare institutions. Methods: The tool utilized criteria developed by clinicians to self-assess IR to deliver four classes of ATMP over a series of time points. Each assessment was independently analyzed and validated by independent expert groups. Results & conclusion: The collated results indicated an overall trend toward IR for all classes of ATMP. The study highlighted areas where IR is evidenced, areas where work is ongoing and areas where further work is required to achieve IR. The study also facilitated validation of the IR assessment tool.


Lupus-like nephritis in an HIV-positive patient: report of a case and review of the literature.
The most common manifestation of HIV/AIDS in the kidney is the collapsing variant of focal segmental glomerular sclerosis, HIV-associated nephropathy (HIVAN). Other forms of renal disease in HIV-infected patients include mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, IgA nephropathy, minimal change disease and proliferative immune-complex GN. We present the case of a 42-year-old Caucasian male with HIV infection, treatment associated peripheral neuropathy, nephrotic syndrome and progressive renal failure. The initial and subsequent kidney biopsies showed diffuse proliferative glomerulonephritis resembling diffuse proliferative (WHO class IV) lupus nephritis. There was no clinical or serological evidence of systemic lupus erythematosus (SLE). Proteinuria improved with ACE-inhibitors, and renal function remained relatively stable while receiving highly active antiretroviral therapy (HAART). A precipitous decline in renal function to end-stage renal disease followed a brief period of withdrawal from potent antiretroviral therapy during which the viral load rebounded. Considering previously reported cases, it appears that lupus-like nephritis is a rare but well-defined pattern of immune-complex-induced renal injury seen in HIV-infected patients. It appears to be markedly responsive to HAART.


Incidence of perinephric hematoma after percutaneous nephrolithotomy.
To identify the incidence of, risk factors for, and subsequent complications of perinephric hematomas after percutaneous nephrolithotomy. We retrospectively analyzed patients who had undergone CT within 5 days of surgery for evidence of perinephric hematomas. Hematoma severity was graded on a 4-point system in which 0 = no blood, 1 = subcapsular blood, 2 = perinephric blood that does not or minimally displaces the kidney, 3 = blood that displaces the kidney > 2 cm, and 4 = blood that extends into the retroperitoneum. Univariate analysis was performed to identify significant preoperative, intraoperative, or postoperative risk factors. A total of 202 patients underwent percutaneous nephrolithotomy and were imaged with CT within 5 days of surgery. Of these, 140 (69%) were grade 0, 55 (27.2%) had localized bleeding (grades 1 or 2), and 7 (3.5%) had extensive bleeding (grades 3 or 4). Complications developed postoperatively in 13 of the patients in groups 1 to 4, including persistent fever longer than 12 hours after surgery in 8 patients, ileus in 2 patients, transfusion of packed red blood cells in 2 patients, and hydrothorax necessitating a chest tube in 1 patient. No patient had surgical or percutaneous intervention. At 3-month follow-up, no patients had symptoms or needed further imaging. Placement of a ureteral stent at the conclusion of the procedure occurred in a significantly higher number of patients in groups 1 to 4 (P = 0.009). The remaining factors were not significantly different. Subset analysis revealed a significantly greater hemoglobin decline in patients with extensive hematomas, groups 3 and 4, compared with groups 0 to 2 (P = 0.001). Perinephric hematomas occur in nearly one-third of patients undergoing percutaneous nephrolithotomies but are extensive only 11% of the time. Hematomas are not associated with an increased incidence of clinically relevant complications. There does not appear to be any indication for serial imaging during hospitalization or at 3-month follow-up.


Vibrio cholerae VciB promotes iron uptake via ferrous iron transporters.
Vibrio cholerae uses a variety of strategies for obtaining iron in its diverse environments. In this study we report the identification of a novel iron utilization protein in V. cholerae, VciB. The vciB gene and its linked gene, vciA, were isolated in a screen for V. cholerae genes that permitted growth of an Escherichia coli siderophore mutant in low-iron medium. The vciAB operon encodes a predicted TonB-dependent outer membrane receptor, VciA, and a putative inner membrane protein, VciB. VciB, but not VciA, was required for growth stimulation of E. coli and Shigella flexneri strains in low-iron medium. Consistent with these findings, TonB was not needed for VciB-mediated growth. No growth enhancement was seen when vciB was expressed in an E. coli or S. flexneri strain defective for the ferrous iron transporter Feo. Supplying the E. coli feo mutant with a plasmid encoding either E. coli or V. cholerae Feo, or the S. flexneri ferrous iron transport system Sit, restored VciB-mediated growth; however, no stimulation was seen when either of the ferric uptake systems V. cholerae Fbp and Haemophilus influenzae Hit was expressed. These data indicate that VciB functions by promoting iron uptake via a ferrous, but not ferric, iron transport system. VciB-dependent iron accumulation via Feo was demonstrated directly in iron transport assays using radiolabeled iron. A V. cholerae vciB mutant did not exhibit any growth defects in either in vitro or in vivo assays, possibly due to the presence of other systems with overlapping functions in this pathogen.


Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis.
Huntington's Disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by cognitive, behavioral and motor dysfunctions. HD is caused by a CAG repeat expansion in exon 1 of the HD gene that is translated into an expanded polyglutamine tract in the encoded protein, huntingtin (HTT). While the most significant neuropathology of HD occurs in the striatum, other brain regions are also affected and play an important role in HD pathology. To date there is no cure for HD, and recently strategies aiming at silencing HTT expression have been initiated as possible therapeutics for HD. However, the essential functions of HTT in the adult brain are currently unknown and hence the consequence of sustained suppression of HTT expression is unpredictable and can potentially be deleterious. Using the Cre-loxP system of recombination, we conditionally inactivated the mouse HD gene homologue at 3, 6 and 9 months of age. Here we show that elimination of Htt expression in the adult mouse results in behavioral deficits, progressive neuropathological changes including bilateral thalamic calcification, and altered brain iron homeostasis.


[Secondary effects of opioids administered by the regional route].
The administration of narcotics in the subarachnoid or the epidural space is gaining acceptance for postoperative pain relief. However, the potential side effects of intrathecal and epidural use of opioids are the following: early and late respiratory depression, pruritus, nausea and vomiting, urinary retention. Early respiratory depression is low and may occur 6 or 12 hours after the epidural narcotics injection. Many factors contribute to the delayed phase of breathing disorders and a close respiratory monitoring is needed during at least 24 hours after epidural morphine injection. Naloxone can be used to reverse the depression. Pruritus can occur in 10 to 30% of patients receiving morphine; 10 to 30% nausea and vomiting, and urinary retention occurs in 20 to 50% of patients.


Vaccination against malaria with live parasites.
Despite nearly 80 years of vaccine research and control efforts, malaria remains one of the most prevalent of all infectious diseases. The fact that people living in regions in which malaria is endemic eventually develop immunity to the parasite and the disease suggest that it might be possible to develop vaccines against malaria. Although few vaccination trials were conducted with whole parasites, the only protocol that leads to the induction of sterile immunity in humans relies on immunization with attenuated parasites. This observation has spurred the search for subunit vaccines that aim to reproduce this protection. As yet, none of the current candidate subunit vaccines have achieved complete protection reproducibly. This failure, coupled with the recent advent of the genetically modified Plasmodium parasites, has led to a renewed interest in the use of live parasites for vaccination. This article reviews past studies, summarizes recent developments in this field and discusses the challenges to be overcome before mass immunization with live parasites could be envisaged.


Alkyl decorated metal-organic frameworks for selective trapping of ethane from ethylene above ambient pressures.
The trapping of paraffins is beneficial compared to selective olefin adsorption for adsorptive olefin purification from a process engineering point of view. Here we demonstrate the use of a series of Zn2(X-bdc)2(dabco) (where X-bdc2- is bdc2- = 1,4-benzenedicarboxylate with substituting groups X, DM-bdc2- = 2,5-dimethyl-1,4-benzenedicarboxylate or TM-bdc2- = 2,3,5,6-tetramethyl-1,4-benzenedicarboxylate and dabco = diazabicyclo[2.2.2.]octane) metal-organic frameworks (MOFs) for the adsorptive removal of ethane from ethylene streams. The best performing material from this series is Zn2(TM-bdc)2(dabco) (DMOF-TM), which shows a high ethane uptake of 5.31 mmol g-1 at 110 kPa, with a good IAST selectivity of 1.88 towards ethane over ethylene. Through breakthrough measurements a high productivity of 13.1 L kg-1 per breakthrough is revealed with good reproducibility over five consecutive cycles. Molecular simulations show that the methyl groups of DMOF-TM are forming a van der Waals trap with the methylene groups from dabco, snuggly fitting the ethane. Further, rarely used high pressure coadsorption measurements, in pressure regimes that most scientific studies on hydrocarbon separation on MOFs ignore, reveal an increase in ethane capacity and selectivity for binary mixtures with increased pressures. The coadsorption measurements reveal good selectivity of 1.96 at 1000 kPa, which is verified also through IAST calculations up to 3000 kPa. This study overall showcases the opportunities that pore engineering by alkyl group incorporation and pressure increase offer to improve hydrocarbon separation in reticular materials.


Up-regulated thromboxane production in the rat liver with biliary obstruction does not contribute to promote hepatic injury.
This study sought to determine whether in vivo inhibition of thromboxane A2 (TXA2) action contribute to attenuate hepatic damage after bile duct ligation (BDL). Male Wistar rats were assigned to sham operation or BDL. At the time of operation, infusion pump with saline, ozagrel natrium (TXA2 synthase inhibitor), or SQ29548 (TXA2 receptor antagonists) was implanted in the abdominal cavity. Plasma alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and total bilirubin levels were measured at 4 days after the operation. The levels of plasma TXB2, a stable metabolite of TXA2, were significantly increased after BDL. Gene expression of TXA2 synthase was also significantly upregulated in the liver. Nonetheless, either an inhibition of TXA2 synthesis by ozagrel natrium or a blockade of TXA2 receptor by SQ29548 has no effect in every measured parameter related to hepatic function. These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats.


A comparative study on proteins released from metaphase chromosomes after digestion with restriction endonucleases and deoxyribonuclease I.
Extensive digestion of Chinese hamster metaphase chromosomes with Alu I, Hae III and Hinf I released up to 40 distinct chromosomal proteins. Some of the proteins released by Hae III or Hinf I were enriched in the protein moiety liberated by Alu I but several proteins released by Hae III were not released by Alu I digestion. The amount of chromosomal protein released by deoxyribonuclease I (DNase I) was comparable to that liberated by the three restriction enzymes so far tested, while only four abundant protein species were detectable in the protein moiety released by DNase I. Two of them with molecular weights of 58,000 and 50,000 were also released by the three restriction enzymes and are similar in size to those found previously in the core-like structure of histone-depleted chromosomes.


Effect of body fat mass and nutritional status on 24-hour leptin profiles in ewes.
This study was designed to determine the effect of feeding or fasting of fat or thin ewes on 24-h leptin profiles. Ewes were assigned, based on ultrasonic assessments of last-rib subcutaneous fat measurements, into fat (fat thickness > 1 cm; mean = 1.52 +/- 0.03 cm; range 1.14 to 2.18 cm) or thin (fat thickness < 1 cm; mean = 0.25 +/- 0.03 cm; range 0.03 to 0.84 cm) groups. Fat and thin ewes were then assigned to either fed or fasted (deprived of feed) groups consisting of five ewes per group. Thus, four groups existed and were designated as fat-fed, fat-fasted, thin-fed, and thin-fasted. Fed ewes had ad libitum access to feed throughout the study. Fasted ewes were prohibited access to feed beginning 48 h preceding the experiment. Plasma samples were collected for leptin analysis from ewes every 15 min for 24 h beginning 48 h after the initiation of feed restriction or the congruent interval in fed ewes. Data were subjected to CLUSTER pulse analysis procedures. Profiles of plasma concentrations of leptin were episodic in nature and did not differ in a diurnal manner. Fed ewes had greater mean concentrations of leptin, area under the curve, number of peaks, peak height, peak nadir, and a shorter interval between peaks than fasted ewes (P < or = 0.05). Fat ewes had greater mean concentrations of leptin, area under the curve, number of peaks, peak height, peak nadir, and a shorter interval between peaks than thin ewes (P < 0.02). There also was a tendency for a body condition x treatment interaction for number of peaks (P = 0.073) and interval between peaks (P = 0.056). These results provide evidence that plasma concentrations of leptin are episodic in nature and are influenced by nutritive state and fat thickness over the ribs, but display no circadian variation.


The therapeutic potential of dopamine modulators on the cardiovascular and renal systems.
In the periphery, physiological dopamine increases renal blood flow, decreases renal resistance and acts on the kidney tubule to enhance natriuresis and diuresis. The loss of dopamine function may be involoved in the deterioration in kidney function associated with ageing and may have a role in the pathogenesis of hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in the treatment of acute heart failure and cardiogenic shock and as a diuretic in renal failure. The clinical uses of dopamine are limited, as it must be given intravenously, and also has widespread effects. The levels of peripheral dopamine can be increased by the administration of L-dopa to increase synthesis, prodrugs to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may be useful in patients with low cardiac output syndrome after cardiac surgery and in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2 receptors, which may retard the progression of chronic renal failure. Glu-dopa is selective for the kidney, thus avoiding widespread side effects. The early clinical studies with ibopamine as a diuretic in heart failure were favourable but the subsequent large mortality study showed that ibopamine increased mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous fenoldopam may be useful in the treatment of hypertension associated with coronary artery bypass surgery or in hypertensive emergencies. Although our understanding of physiological and pathological roles of peripheral dopamine has been increasing rapidly in recent times, we still need more information to allow the design of clinically useful drugs that modify these roles. One priority is an orally-active selective dopamine D1 receptor agonist.


Hepatocarcinogenesis in transgenic mice carrying albumin-promoted SV40 T antigen gene.
We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas at around 5 months and die of liver insufficiency by 7 months. Sequential morphological observation of hepatocarcinogenesis revealed 5 distinct stages: (I) newborn to 2 weeks of age, neither recognizable histological changes nor cellular replication in spite of T antigen expression; (II) between 3 and 7 weeks, diffuse cytomegalic change of hepatocytes with numerous abnormal mitoses, usually resulting in cell death; (III) from 7 weeks onwards, quasi-regenerative small hepatocyte foci with a decreased tendency for cytomegaly in spite of T antigen expression, rapidly replacing the hepatic tissue; (IV) 11 weeks of age and thereafter, neoplastic foci and nodules with enzymatic alteration; (V) 20 weeks of age and thereafter, gross hepatocellular carcinomas with occasional pulmonary metastases. Considerable variation existed both in morphological and enzymatic features and T antigen expression among neoplastic lesions, including carcinomas. Thus, these transgenic mice clearly show a multistep process in hepatocarcinogenesis with remarkable synchrony and provide a promising model for analyzing the essential events of carcinogenesis at different stages.


Application of laparospic ultrasonography in surgery of small renal cell carcinoma.
: To assess the clinic value of application of laparospic ultrasonography (LU) in partial nephrectomy of small renal cell carcinoma. From 2007 to 2011, 28 small renal cell carcinoma patients in ou clinic underwent laparoscopic partial nephrectomy with LU. For comparison with preoperative conventional ultrasound and CT, we collected ultrasonic performance of the affected side kidney, renal tumor location, size, echo change, blood supply situation and the relationship with the surrounding tissue. LU could more clearly show the tumor interior structure and blood supply, as well as the relationship with the surrounding tissue. It also can provided doctor assistance with real-time tumor resection, reducing operative complications. LU can clearly show tumor internal structure and blood supply, which is helpful for explicit diagnosis. Moreover, it supplies accurate information for surgeons and assists surgery. Therefore LU has an important guiding value in partial nephrectomy for small renal cell carcinoma.


Combinatorial fabrication of composite nanorods using oblique angle co-deposition.
We demonstrate that oblique angle co-deposition can be used as a versatile combinatory nanofabrication technique to generate a library of nanomaterials. Using the Cu-Fe2O3 system as an example, by carefully characterizing the vapor plumes of the source materials, a composition map can be generated, which is used to design the locations of all the substrate holders. The resulting nanostructures at different locations show different thickness, morphology, crystallinity, composition, as well as inhomogeneity in microstructures, and material maps of all these structural parameters are established. By further oxidizing or reducing the composite nanostructures, their properties-such as band gap, photocatalytic performance, and magnetic properties-can be easily linked to their composition and other structural parameters. Optimal materials for photocatalytic and magnetic applications are efficiently identified. It is expected that oblique angle co-deposition and its variations could become the most powerful combinatory nanofabrication technique for nanomaterial survey.


[Juvenile malignant lymphomas. 1. Hodgkin's lymphoma].
From 1970 to 1978 22 children with Hodgkin's lymphomas at the age of 4-15 years were treated at the university children's hospital of Jena. There were 16 patients with the first appearance of the disease and 6 with relapses. The stage classification was carried out after the Ann-Arbor-classification. A "staging" operation with laparotomy and splenectomy was performed in 17 children. The histological material was classified after the Rye-modification of the Lukes-Butler-classification. The clinical staging showed 8 patients in stage I, 7 in stage II, 6 in stage III and one child was in stage IV. The therapy consisted of a telecobalt irradiation extended field irradiation, total nodular and local irradiation) with a focal dose of 4500 rad and a chemotherapy (6 cycles COPP). The life-table-analysis for those patients who were primarily treated in Jena showed a complete five-year-remission rate of 92 per cent. The five-year-survival-rate for all patients (with the first appearance of the disease and with relapses) amounts to 77 per cent. After splenectomy we observed two overwhelmingly progressing aetiologically not clear infections and a pneumococcal meningitis.


[Surgical treatment of primary lung cancer in women].
Among 1906 lung carcinoma cases treated in the clinic up to 1975 inclusive, there were 182 women (9.5%). The comparative study of 84 women and 927 men operated upon, proved the operability and resectability in women (46.1% +/- 3.7 and 34.1 +/- 3.5) to be lower than in men (53.8% +/- 1.2 and 46.3% +/- 1.2). Peripheral cancer was found in 28.6% +/- 3.3 of women and in 23.6% +/- 1.0 of men. The main histological form of the tumor in women was glandular carcinoma (45.2% +/- 6.3) and in men squamous cell carcinoma (62.2% +/- 1.7). The lobectomy was the most common of radical operations performed in women (58.1% +/- 6.2); in men it was the pneumectomy (65.1% +/- 1.7). In 6 of 26 women suffering from neoplasm of stage III the vast pneumectomy was carried out; in men this operation constituted 46.1% of all cases of total lung removal. The immediate results in women (complications--14.3% +/- 8.8 and mortality--2.4% +/- 1.7) are better than in men (24.1% +/- 1.4 and 9.3% +/- 1.0). The five-year follow-up showed the survival in women to be 39.1% +/- 10.6 and in men 28.3% +/- 3.0.


A novel HPLC-based approach makes possible the spatial characterization of cellular PtdIns5P and other phosphoinositides.
PtdIns5P was discovered in 1997 [Rameh, Tolias, Duckworth and Cantley (1997) Nature 390, 192-196], but still very little is known about its regulation and function. Hitherto, studies of PtdIns5P regulation have been hindered by the inability to measure cellular PtdIns5P using conventional HPLC, owing to poor separation from PtdIns4P. In the present paper we describe a new HPLC method for resolving PtdIns5P from PtdIns4P, which makes possible accurate measurements of basal and inducible levels of cellular PtdIns5P in the context of other phosphoinositides. Using this new method, we found that PtdIns5P is constitutively present in all cells examined (epithelial cells, fibroblasts and myoblasts, among others) at levels typically 1-2% of PtdIns4P levels. In the beta-pancreatic cell line BTC6, which is specialized in insulin secretion, PtdIns5P levels were higher than in most cells (2.5-4% of PtdIns4P). Using subcellular fractionation, we found that the majority of the basal PtdIns5P is present in the plasma membrane, but it is also enriched in intracellular membrane compartments, especially in SER (smooth endoplasmic reticulum) and/or Golgi, where high levels of PtdIns3P were also detected. Unlike PtdIns3P, PtdIns5P was also found in fractions containing very-low-density vesicles. Knockdown of PIP4K (PtdIns5P 4-kinase) leads to accumulation of PtdIns5P in light fractions and fractions enriched in SER/Golgi, whereas treatment with Brefeldin A results in a subtle, but reproducible, change in PtdIns5P distribution. These results indicate that basal PtdIns5P and the PtdIns5P pathway for PtdIns(4,5)P(2) synthesis may play a role in Golgi-mediated vesicle trafficking.


Agronomic performance and remote sensing assessment of organic and mineral fertilization in rice fields.
Rice heavily relies on nitrogen fertilizers, posing environmental, resource, and geopolitical challenges. This study explores sustainable alternatives like animal manure and remote sensing for resource-efficient rice cultivation. It aims to assess the long-term impact of organic fertilization and remote sensing monitoring on agronomic traits, yield, and nutrition. A six-year experiment in rice fields evaluated fertilization strategies, including pig slurry (PS) and chicken manure (CM) with mineral fertilizers (MIN), MIN-only, and zero-fertilization. Traits, yield, spectral responses, and nutrient content were measured. Sentinel-2 remote sensing tracked crop development. Cost-effective organic fertilizers (PS and CM) caused a 13% and 15% yield reduction but still doubled zero-fertilization yield. PS reduced nitrogen leaching. Heavy metals in rice grains were present at safe amounts. Organic-fertilized crops showed nitrogen deficiency at the late vegetative stages, affecting yield. Sentinel-2 detected nutrient deficiencies through NDVI. Organic fertilizers, especially PS, reduce nitrogen loss, benefiting the environment. However, they come with yield trade-offs and nutrient management challenges that can be managed and balanced with reduced additional mineral applications. Sentinel-2 remote sensing helps manage nutrient deficiencies. In summary, this research favors cost-effective organic fertilizers with improved nutrient management for sustainable rice production.


Effects of fir-wood biochar on CH4 oxidation rates and methanotrophs in landfill cover soils packed at three different proctor compaction levels.
Application of biochar to landfill cover soils can purportedly improve methane (CH4) oxidation rates, but understanding the combined effects of soil texture, compaction, and biochar on the activity and composition of the methanotrophs is limited. The amendment of wood biochar on two differently textured landfill cover soils at three compaction levels of the Proctor density was explored by analyzing changes in soil physical properties relevant to methane oxidation, the effects on CH4 oxidation rates, and the composition of the methanotrophic community. Loose soils with and without biochar were pre-incubated to equally elevate the CH4 oxidation rates. Hereafter, soils were compacted and re-incubated. Methane oxidation rates, gas diffusivity, water retention characteristics, and pore size distribution were analyzed on the compacted soils. The relative abundance of methanotrophic bacteria (MOB) was determined at the end of both the pre-incubation and incubation tests of the packed samples. Biochar significantly increased porosity at all compaction levels, enhancing diffusion coefficients. Also, a re-distribution in pore sizes was observed. Increased gas diffusivity from low compaction and amendment of biochar, though, did not reflect higher methane oxidation rates due to high diffusive oxygen fluxes over the limited height of the compacted soil specimens. All soils, with and without biochar, were strongly dominated by Type II methanotrophs. In the sandy soil, biochar amendment strongly increased MOB abundance, which could be attributed to a corresponding increase in the relative abundance of Methylocystis species, while no such response was observed in the clayey soil. Compaction did not change the community composition in either soil. Fir-wood biochar addition to landfill cover soils may not always enhance methanotrophic activity and hence reduce fugitive methane emissions, with the effect being soil-specific. However, especially in finer and more compacted soils, biochar amendment can maintain soil diffusivity above a critical level, preventing the collapse of methanotrophy.


Shear Thinning and Nonlinear Structural Deformation of Ionic Liquids with Long Alkyl Chains Studied by Molecular Dynamics Simulation.
Nonequilibrium molecular dynamics (MD) simulation was performed on imidazolium-based ionic liquids of two different alkyl chain lengths, and shear-rate-dependent viscosity was evaluated. Compared with the frequency-dependent linear shear viscosity determined by equilibrium MD simulation, shear thinning occurs at the shear rate several times lower than that predicted by the Cox-Merz rule. The deformation of the structure factor was also evaluated as the function of shear rate. The onset of shear thinning corresponds to that of the nonlinearity in the deformation of the charge-alternation mode in both ionic liquids, which is in harmony with the result of our previous work that the shear relaxation of ionic liquids is mainly coupled to the structural relaxation of the charge-alternation mode. In the presence of the polar-nonpolar domain structure characteristic to ionic liquids with a long alkyl chain, in particular, the nonlinearity in the domain mode begins within the Newtonian regime of shear viscosity.


Comparison of post-operative outcomes of graft materials used in reconstruction of blow-out fractures.
Trauma to the face caused by assault or impact may cause internal orbital fracture. Increased intraorbital pressure without disruption of soft tissue integrity or causing a fracture line in orbital rims or orbital floor fractures described as 'orbital blow-out fracture'. Such fractures have been categorized as 'pure blow-out fractures' in which only the orbital floor is affected, and 'impure blow-out fractures' in which other maxillofacial bones such as zygoma, maxilla and nasoethmoid are also affected. Physical examination reveals periorbital edema and ecchymosis, subconjunctival hemorrhage, limitation of eye globe movements, diplopia, enophthalmos, dystopia, and infraorbital hypoesthesia. Reconstruction of the orbital bony structures is the most important issue to preserve the standard orbital functions and providing an aesthetic view. Although many surgical approaches have been defined in the literature regarding the attitude and timing of treatment, no consensus exists. In literature; many autogenous and alloplastic biomaterials have been recommended to correct orbital bone defects. This study aims to compare postoperative outcomes of patients presenting with pure and impure blow-out fractures repaired with cartilage, bone grafts, titanium mesh or porous polyethylene implant. Sixty-four orbital floor fractures of 62 cases were included in this research who admitted to our clinic with maxillofacial trauma between 2011 and 2018. All patients underwent maxillofacial radiological examination; Waters radiography and also axial-coronal plane maxillofacial and orbital computerized tomography. Permanent, post-operative, vertical diplopia in extreme gazes was detected in 3 of 14 patients in whom the orbital floor was reconstructed with an iliac bone graft. Two of nineteen cases who underwent reconstruction using auricular conchal cartilage graft had vertical diplopia in extreme gazes four months after the operation. The implant extruded and became palpable in 2 of 15 patients in the porous polyethylene implant group. None of the patients in the iliac bone and conchal cartilage autograft groups was presented late postoperative enophthalmos according to the graft resorption. In titanium mesh group, 1 of eleven patients had permanent, post-operative vertical diplopia in extreme gazes. None of the patients in this group developed any donor area complications, infection, or implant extrusion. Results show that the auricular conchal cartilage graft was the best biomaterial used to repair defects smaller than 4 cm², where as titanium mesh was a good option to repair defects larger than 4 cm². However, selection of the optimal biomaterial to be used to repair orbital blow-out fractures should be made according to patient characteristics and preoperative findings, the severity of the injury, the cost of the biomaterial to be used, and surgeon's expertise.


Encephalitis Lethargica With Isolated Substantia Nigra Lesions Followed by a Second Encephalitis in a Child With Humoral Immunodeficiency.
Encephalitis lethargica is an encephalitic illness with multiple nervous system symptoms. Lesions only involving substantia nigra on magnetic resonance imaging are uncommon, especially in children. A second encephalitis illness after encephalitis lethargica has never been reported before. We describe a 7-year-old boy with humoral immunity deficiency who developed encephalitis lethargica associated with bilateral substantia nigra lesions on magnetic resonance imaging. After a nearly complete recovery, he developed encephalitis once again. He was diagnosed with encephalitis lethargica with somnolence, akinetic mutism, and ophthalmoplegia after intermittent fever. Cerebrospinal fluid pleocytosis and positive oligoclonal bands were documented. Symmetrical substantia nigra lesions on high-intensity magnetic resonance imaging gradually evolved into a liquid signal. He had almost recovered when he developed fatigue and hypersomnia and was diagnosed with encephalitis again, supported by mild pleocytosis in cerebrospinal fluid and subcortical white matter lesions in the frontal lobes. His symptoms resolved following administration of corticosteroids and immunoglobulins. This is the first report of an immune-deficient child to develop encephalitis lethargica with isolated substantia nigra lesions on magnetic resonance imaging and a second encephalitis illness after recovery from encephalitis lethargica.


Endoscopic Evaluation of Upper and Lower Gastro-Intestinal Bleeding.
A myriad of pathologies lead to gastro-intestinal bleeding (GIB). The common clinical presentations are hematemesis, melena, and hematochezia. Endoscopy aids localization and treatment of these lesions. The aim was to study the differential diagnosis of GIB emphasizing the role of endoscopy in diagnosis and treatment of GIB. A prospective study of patients with GIB referred to the Endoscopy unit of two health facilities in Port Harcourt Nigeria from February 2012 to August 2014. The variables studied included: Demographics, clinical presentation, risk score, endoscopic findings, therapeutic procedure, and outcome. Data were collated and analyzed using SPSS version 20 software. A total of 159 upper and lower gastro-intestinal (GI) endoscopies were performed during the study period with 59 cases of GI bleeding. There were 50 males and 9 females with an age range of 13-86 years (mean age 52.4 ± 20.6 years). The primary presentations were hematochezia, hematemesis, and melena in 44 (75%), 9 (15%), and 6 (10%) cases, respectively. Hemorrhoids were the leading cause of lower GIB seen in 15 cases (41%). The majority of pathologies in upper GIB were seen in the stomach (39%): Gastritis and benign gastric ulcer. Injection sclerotherapy was successfully performed in the hemorrhoids and a case of gastric varices. The mortality recorded was 0%. Endoscopy is vital in the diagnosis and treatment of GIB. Gastritis and Haemorrhoid are the most common causes of upper and lower GI bleeding respectively, in our environment.


A nucleotide that enhances the charging of RNA minihelix sequence variants with alanine.
We showed earlier that a single G3.U70 base pair within the amino acid acceptor helix is a major determinant of the identity of tRNA(Ala). In addition, we demonstrated that an RNA hairpin minihelix that recreates the 12 base pair acceptor-T psi C stem of tRNA(Ala) is also aminoacylated in a G3.U70-dependent manner. Determinants for efficient aminoacylation at pH 7.5 have been further investigated with minihelix substrates that have sequence variations at 3.70 and other locations. Although a U,U mismatch and other 3.70 nucleotide alternatives to G.U were recently proposed by others as also important for alanine acceptance, neither that mismatch nor any of four other 3.70 nucleotide combinations confer aminoacylation in vitro with alanine, even with substrate levels of enzyme. In contrast, permutations of the so-called discriminator nucleotide N73 (at position 73) strongly modulate, but do not block, aminoacylation of those substrates that encode G3.U70. In particular, the efficiency of G3.U70-dependent aminoacylation with alanine is strongly enhanced by having the wild-type A73. The effect of N73 alone can explain most of the difference in aminoacylation efficiency of a G3.U70-containing tRNA and a minihelix substrate whose sequences vary significantly from their tRNA(Ala) counterparts. Comparison with earlier work suggests that the substantial modulating effect of N73 is partly or completely obscured when N73 tRNA variants are expressed as amber suppressors in vivo.


Preventing diabetic foot ulcer recurrence in high-risk patients: use of temperature monitoring as a self-assessment tool.
The purpose of this study was to evaluate the effectiveness of a temperature monitoring instrument to reduce the incidence of foot ulcers in individuals with diabetes who have a high risk for lower extremity complications. In this physician-blinded, randomized, 15-month, multicenter trial, 173 subjects with a previous history of diabetic foot ulceration were assigned to standard therapy, structured foot examination, or enhanced therapy groups. Each group received therapeutic footwear, diabetic foot education, and regular foot care. Subjects in the structured foot examination group performed a structured foot inspection daily and recorded their findings in a logbook. If standard therapy or structured foot examinations identified any foot abnormalities, subjects were instructed to contact the study nurse immediately. Subjects in the enhanced therapy group used an infrared skin thermometer to measure temperatures on six foot sites each day. Temperature differences >4 degrees F (>2.2 degrees C) between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized. The enhanced therapy group had fewer foot ulcers than the standard therapy and structured foot examination groups (enhanced therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs. structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy and structured foot examination groups were 4.37 and 4.71 times more likely to develop ulcers than patients in the enhanced therapy group. Infrared temperature home monitoring, in serving as an "early warning sign," appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.


Progress in genotyping of Chlamydia trachomatis.
To review the common genotyping techniques of Chlamydia trachomatis in terms of their principles, characteristics, applications and limitations. Data used in this review were mainly from English literatures of PubMed database. The search terms were "Chlamydia trachomatis" and "genotyping". Meanwhile, data from World Health Organization were also cited. Original articles and reviews relevant to present review's theme were selected. Different genotyping techniques were applied on different occasions according to their characteristics, especially in epidemiological studies worldwide, which pushed the study of Chlamydia trachomatis forward greatly. In addition, summaries of some epidemiological studies by genotyping were also included in this work for reference and comparison. A clear understanding of common genotyping techniques could be helpful to genotype C. trachomatis more appropriately and effectively. Furthermore, more studies on the association of genotypes of Chlamydia trachomatis with clinical manifestations should be performed.


Brain glucose uptake is associated with endogenous glucose production in obese patients before and after bariatric surgery and predicts metabolic outcome at follow-up.
To investigate further the finding that insulin enhances brain glucose uptake (BGU) in obese but not in lean people by combining BGU with measures of endogenous glucose production (EGP), and to explore the associations between insulin-stimulated BGU and peripheral markers, such as metabolites and inflammatory markers. A total of 20 morbidly obese individuals and 12 lean controls were recruited from the larger randomized controlled SLEEVEPASS study. All participants were studied under fasting and euglycaemic hyperinsulinaemic conditions using fluorodeoxyglucose-positron emission tomography. Obese participants were re-evaluated 6 months after bariatric surgery and were followed-up for ~3 years. In obese participants, we found a positive association between BGU and EGP during insulin stimulation. Across all participants, insulin-stimulated BGU was associated positively with systemic inflammatory markers and plasma levels of leucine and phenylalanine. Six months after bariatric surgery, the obese participants had achieved significant weight loss. Although insulin-stimulated BGU was decreased postoperatively, the association between BGU and EGP during insulin stimulation persisted. Moreover, high insulin-stimulated BGU at baseline predicted smaller improvement in fasting plasma glucose at 2 and 3 years of follow-up. Our findings suggest the presence of a brain-liver axis in morbidly obese individuals, which persists postoperatively. This axis might contribute to further deterioration of glucose homeostasis.


Plant-derived micronutrients suppress monocyte adhesion to cultured human aortic endothelial cell layer by modulating its extracellular matrix composition.
Monocyte adhesion to endothelium plays an important role in atherosclerosis. We investigated the effects of micronutrients on monocyte-binding properties of extracellular matrix (ECM) produced by human aortic endothelial cells (AoEC). Confluent cultures of AoEC were exposed to ascorbic acid, quercetin, gotu kola extract (10% asiatic acid), green tea extract (40% epigallocatechin gallate), or a mixture of these micronutrients for 48 hours. AoEC-produced ECM was exposed by differential treatment. U937 monocyte adhesion was assayed by fluorescence. ECM composition was assayed immunochemically and with radiolabeled metabolic precursors. AoEC exposure to micronutrients reduced ECM capacity to bind monocytes in a dose-dependent manner. This effect was accompanied by profound changes in the ECM composition. Correlation analysis revealed that changes in monocyte adhesion to ECM had the strongest positive correlation with ECM content for laminin (CC = 0.9681, P < 0.01), followed by fibronectin, collagens type III, I, and IV, biglycan, heparan sulfate, and elastin. The strongest negative correlation was with chondroitin sulfate (CC = -0.9623, P < 0.01), followed by perlecan and versican. Individual micronutrients had diverse effects on ECM composition and binding properties, and their mixture was the most effective treatment. In conclusion, micronutrient-dependent reduction of monocyte adhesion to endothelium is partly mediated through specific modulation of ECM composition and properties.


Microbiome and pancreatic cancer: A comprehensive topic review of literature.
To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes. A comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016. Diverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations. Pilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival.


Are there theory of mind regions in the brain? A review of the neuroimaging literature.
There have been many functional imaging studies of the brain basis of theory of mind (ToM) skills, but the findings are heterogeneous and implicate anatomical regions as far apart as orbitofrontal cortex and the inferior parietal lobe. The functional imaging studies are reviewed to determine whether the diverse findings are due to methodological factors. The studies are considered according to the paradigm employed (e.g., stories vs. cartoons and explicit vs. implicit ToM instructions), the mental state(s) investigated, and the language demands of the tasks. Methodological variability does not seem to account for the variation in findings, although this conclusion may partly reflect the relatively small number of studies. Alternatively, several distinct brain regions may be activated during ToM reasoning, forming an integrated functional "network." The imaging findings suggest that there are several "core" regions in the network-including parts of the prefrontal cortex and superior temporal sulcus-while several more "peripheral" regions may contribute to ToM reasoning in a manner contingent on relatively minor aspects of the ToM task.


Bacterial arthropod-borne diseases in West Africa.
Arthropods such as ticks, lice, fleas and mites are excellent vectors for many pathogenic agents including bacteria, protozoa and viruses to animals. Moreover, many of these pathogens can also be accidentally transmitted to humans throughout the world. Bacterial vector-borne diseases seem to be numerous and very important in human pathology, however, they are often ignored and are not well known. Yet they are in a phase of geographic expansion and play an important role in the etiology of febrile episodes in regions of Africa. Since the introduction of molecular techniques, the presence of these pathogens has been confirmed in various samples from arthropods and animals, and more rarely from human samples in West Africa. In this review, the aim is to summarize the latest information about vector-borne bacteria, focusing on West Africa from 2000 until today in order to better understand the epidemiological risks associated with these arthropods. This will allow health and veterinary authorities to develop a strategy for surveillance of arthropods and bacterial disease in order to protect people and animals.


Oxanilic acids, a new series of orally active antiallergic agents.
A large number of oxanilic acid esters and N-heteroaryl oxamic acid esters were prepared and found to have antiallergic activity using the rat passive cutaneous anaphylaxis (PCA) test. Many of the oxanilic acid esters are active orally, with the most active species having an aryl 2'-carbamoyl group and a 3'-methoxy group. Hydrolysis of the ester from the oxanilic ester moiety causes a loss of oral activity.


Pharmacokinetic consequences of pegylation.
Pegylation, generally described as the molecular attachment of polyethylene glycols (PEGs) with different molecular weights to active drug molecules or surface treatment of drug-bearing particles with PEGs, is one of the most promising and extensively studied strategies with the goal of improving the pharmacokinetic behavior of the therapeutic drugs. A variety of PEGs, both linear and branched, with different molecular weights have been exploited successfully for use in this procedure in the form of reactive PEG species. Both reversible and irreversible PEG-drug conjugates have been prepared with relative advantages/disadvantages. The main pharmacokinetic outcomes of pegylation are summarized as changes occurring in overall circulation life-span, tissue distribution pattern, and elimination pathway of the parent drug/particle. Based on these favorable pharmacokinetic consequences leading to desired pharmacodynamic outcomes, a variety of proteins/peptides as well as small molecule drugs have been pegylated and evaluated successfully. Also a number of corresponding products have been approved by the U.S. FDA for specific clinical indications and some others are underway. In this article, the chemistry, rationale, strategies, pharmacokinetic outcomes, and therapeutic possibilities of pegylated drugs are reviewed with pharmacokinetic aspects presented with more details.


Biases in perceiving gaze vergence.
The focus of another person's gaze is an important cue in social interactions, helping us to understand others' intentions, predict their behavior, and allocate our own attention appropriately. The perception of gaze vergence provides information about the distance at which another person is fixating, but has yet to receive much empirical attention. Here, we report that observers display systematic biases when perceiving others' gaze vergence and depth of fixation. Specifically, they perceive others as having convergent gaze and fixating at closer distances, especially when gaze is directed downward or observed under conditions of sensory uncertainty. These biases may reflect the predominance of convergent over divergent gaze in everyday social interactions and implicit knowledge of the physical structure of the environment, in which objects below our line of sight are typically closer. These findings demonstrate the sophistication of social vision, in which our visual perception of others is shaped by statistical regularities, and help to establish the perception of others' gaze vergence and fixation distance as a subject of psychological investigation. (PsycINFO Database Record


Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice.
Mice carrying a loss-of-function mutation in the klotho gene (KL(-/-) mice) develop ageing-like symptoms around 4 weeks after birth and suffer from multiple age-related disorders observed in humans, including osteoporosis, arteriosclerosis, and pulmonary emphysema. The klotho gene encodes a single-pass transmembrane protein that may function in signaling pathways that suppress ageing. To investigate the ability of Klotho to regulate the development of ageing-related disorders, we established an inducible Klotho expression system using KL(-/-) mice carrying an exogenous klotho gene fused to the mouse metallothionein-I promoter, in which Klotho expression was dependent on zinc water feeding. We demonstrate that many advanced ageing-like KL(-/-) phenotypes were restored to normal whenever Klotho expression was induced. Conversely, decreasing Klotho expression in these rescued KL(-/-) mice induced several ageing-like KL(-/-) phenotypes. Our data indicate that Klotho may be effective in the treatment of multiple age-related disorders and is essential for maintaining animals free of these disorders.


Study on luminescence properties of Eu2+ in BaAl12O19 matrix.
Eu(2+)-doped BaAl12O19 phosphors were prepared using the sol-gel method, and their structure and luminescence properties were characterized by X-ray diffraction (XRD) analysis and fluorescence spectrometry. The results showed that a single hexagonal BaAl12O19 crystal structure was synthesized and the emission spectrum of BaAl12O19:Eu exhibited a broad asymmetric band from 375 to 600 nm, which was composed of three emission peaks at 438, 462, and 511 nm. The effects of crystallization temperature, Eu2+ concentration, and Al3+ content on the occupation of Eu2+ in three crystallographic positions were investigated. The emission intensity of 438 nm increased with increasing crystallization temperature, while the emission intensity of 462 and 511 nm increased with the increase of Eu2+ concentration and Al3+ content.


Molecular genetic methods in the diagnosis of hematologic neoplasms.
Leukemias and lymphomas are monoclonal neoplasms that arise as a result of molecular abnormalities. These abnormalites are diverse but can be grouped into two general categories, chromosomal translocations that usually result in oncogene activation and inactivation of tumor suppressor genes. Recent advances in our understanding of chromosomal translocations have led to improved classification of leukemias and lymphomas. For example, the t(9;22)(q34;q11) is now considered a defining feature of chronic myeloid leukemia, and the t(2;5)(p23;q35) defines a clinically and biologically unique subset of anaplastic large cell lymphomas. In this review, we focus on chromosomal translocations in hematologic neoplasms and the techniques used for their detection. We also briefly discuss tumor suppressor genes and assessment of clonality in lymphoid neoplasms.


Thyrotoxic hypokalemic periodic paralysis triggered by high carbohydrate diet.
Thyrotoxic hypokalemic periodic paralysis is an uncommon disorder characterized by elevated thyroid hormone, muscle weakness or paralysis, and intracellular shifts of potassium leading to hypokalemia. This article presents a case of thyrotoxic hypokalemic periodic paralysis in a 22-year old Hispanic man with nonfamilial thyrotoxic hypokalemic periodic paralysis triggered by a high carbohydrate diet. Laboratory studies showed elevated thyroid hormone, decreased thyroid-stimulating hormone, and hypokalemia. Rapid reduction in thyroid hormone levels by giving antithyroid drugs such as propylthiouracil and prompt potassium therapy with frequent measurements of serum potassium levels during therapy to avoid catastrophic hyperkalemia when potassium starts to shift back from intracellular to extracellular compartments can lead to successful outcome.


Cerebral perfusion impairment in a patient with toluene abuse.
We report the case of a 17-yr-old man diagnosed as a toluene abuser. He had an 8-mo history of toluene inhalation exposure and was admitted to this hospital with symptoms of auditory and visual hallucination. Magnetic resonance imaging (MRI) revealed no structural abnormalities both on T1- and T2-weighted images, whereas SPECT using 99mTc-ethyl cysteinate dimer (ECD) showed multifocally decreased perfusion in the cerebral cortex, basal ganglia and thalami. Our case indicates that SPECT detects early central nervous system injury from toluene inhalation even when neurological examination and neuroanatomic imaging such as MRI are normal.


Effect of incentives for medication adherence on health care use and costs in methadone patients with HIV.
The potential benefits of anti-retroviral therapy for HIV is not fully realized because of difficulties in adherence with demanding treatment regimens, especially among injection drug users. HIV-positive methadone patients who were less than 80% adherent with their primary anti-retroviral therapy were randomized to a trial of incentives for on-time adherence. Adherence was rewarded with an escalating scale of vouchers redeemable for goods. Both intervention and control group visited a medication coach twice a month. The cost of the intervention was determined by micro-costing. Other costs were obtained from administrative data and patient report of out-of-system care. During the 12-week intervention period, the incremental direct cost of the intervention, including treatment vouchers, was $942. The voucher group incurred $2572 in anti-retroviral drug cost, significantly more than the $1973 incurred by the comparison group (p<.01). Adherence, as measured by on-time openings of an electronically monitored vial, was 78% in the intervention group and 56% in the control group. The incremental direct cost of voucher incentives was $292 per month. If the observed increase in adherence from voucher incentives can be sustained in the long-term, the literature suggests that disease progression will be slowed. Further research is needed to evaluate if the improvement can be sustained or achieved at lower cost. Mitigation of treatment resistance and reduction in HIV transmission are additional benefits that favor adoption.


Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.
Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. In this work, we introduce a proteomic assay called decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action. Examples range from detecting DNA damage by chemotherapeutics, to identifying drug-specific PTM signatures of kinase inhibitors, to demonstrating that rituximab kills CD20-positive B cells by overactivating B cell receptor signaling. DecryptM profiling of 31 cancer drugs in 13 cell lines demonstrates the broad applicability of the approach. The resulting 1.8 million dose-response curves are provided as an interactive molecular resource in ProteomicsDB.


Dressed counterions: strong electrostatic coupling in the presence of salt.
We reformulate the theory of strong electrostatic coupling in order to describe an asymmetric electrolyte solution of monovalent salt ions and polyvalent counterions using field-theoretical techniques and Monte Carlo simulations. The theory is based on an asymmetric treatment of the different components of the electrolyte solution. The weak coupling Debye-Hückel approach is used in order to describe the monovalent salt ions while a strong coupling approach is used to tackle the polyvalent counterions. This combined weak-strong coupling approach effectively leads to dressed interactions between polyvalent counterions and thus directly affects the correlation attraction mediated by polyvalent counterions between like-charged objects. The general theory is specifically applied to a system composed of two uniformly charged plane-parallel surfaces in the presence of salt and polyvalent counterions. In the strong coupling limit for polyvalent counterions, the comparison with Monte Carlo simulations shows good agreement for large enough values of the electrostatic coupling parameter. We delineate two limiting laws that in fact encompass all the Monte Carlo data.


Consultant's Playbook: A Survey of Pharmacy Consultant Experiences Among Hospitals In the University HealthSystem Consortium.
Our team surveyed a group of pharmacy directors to learn about their experiences with pharmacy consultants so that the directors might be able to use their consulting resources in a more effective manner. In May 2012, the University HealthSystem Consortium (UHC) Pharmacy Council Financial Performance Committee developed an electronic survey that collectively measured the characteristics, goals, and methodology of historical pharmacy consultant engagements and level of satisfaction. After e-mailing the initial electronic survey, we conducted follow-up telephone interviews with respondents from July through November 2012. These interviews were designed to include questions about expected outcomes, recommendations for evaluation processes, timelines for implementing the recommendations, consultants' expenses, and insights gained. A total of 23 pharmacy directors responded to the initial electronic survey; their organizations had engaged at least one consultant within the previous 5 years. Data were collected for 28 consultant engagements. Subsequent telephone interviews were conducted with 20 of the 23 pharmacy directors (87%) who completed the initial electronic survey, accounting for 25 of the 28 consultant engagements (89%). Cost reduction along with revenue enhancement was most often the focus of these engagements. These engagements were also mainly within the scope of an organization-wide effort initiated by the executive board or executive team. Consultant experiences varied greatly in terms of (1) the degree to which assistance was provided to the organization, (2) benchmarking methodologies and resources, and (3) timelines for implementing the consultants' recommendations. In general, most respondents rated their consultant experience as positive and were able to provide "pearls of wisdom" or lessons learned.


Purification of RNA and RNA-protein complexes by an R17 coat protein affinity method.
We describe an affinity chromatography method to isolate specific RNAs and RNA-protein complexes formed in vivo or in vitro. It exploits the highly selective binding of the coat protein of bacteriophage R17 to a short hairpin in its genomic RNA. RNA containing that hairpin binds to coat protein that has been covalently bound to a solid support. Bound RNA-protein complexes can be eluted with excess R17 recognition sites. Using purified RNA, we demonstrate that binding to immobilized coat protein is highly specific and enables one to separate an RNA of interest from a large excess of other RNAs in a single step. Surprisingly, binding of an RNA containing non-R17 sequences to the support requires two recognition sites in tandem; a single site is insufficient. We determine optimal conditions for purification of specific RNAs by comparing specific binding (retention of RNAs with recognition sites) to non-specific binding (retention of RNAs without recognition sites) over a range of experimental conditions. These results suggest that binding of immobilized coat protein to RNAs containing two sites is cooperative. We illustrate the potential utility of the approach in purifying RNA-protein complexes by demonstrating that a U1 snRNP formed in vivo on an RNA containing tandem recognition sites is selectively retained by the coat protein support.


Strategies adopted to manage physical and psychosocial challenges after returning home among people with stroke: A qualitative study.
Stroke survivors encounter various physical and psychosocial challenges after hospital discharge. Systematic reviews consistently suggest the importance of self-management in promoting post-stroke recovery. However, stroke survivors' performance of self-management behaviors after returning home is poorly understood. This study was conducted to explore how stroke survivors manage their life after returning home from the hospital. This was a qualitative study with individual, semi-structured interviews. We recruited a purposive sample of adults who had a first or recurrent ischemic or hemorrhagic stroke and currently lived at home. Participants were asked about their post-stroke experiences, challenges encountered, and strategies adopted for managing post-stroke conditions. Data were transcribed verbatim and analyzed using thematic analysis. A total of 30 stroke survivors (mean age = 61.97 years, SD = 10.20) were interviewed. Most were men (n = 18), married (n = 25), and retired (n = 21). Two-thirds had experienced an ischemic stroke. Five key themes emerged: pursuing lifelong learning to live well after a stroke; reinterpreting unpleasant experiences as new learning opportunities; engaging in life activities to better adapt to post-stroke challenges; being confident in oneself to persevere in self-management behaviors; and continuing to accept the current self and explore the new self. Participants regarded learning as a prerequisite for improving their affected functions and managing uncertainties in recovery. Learning requires self-participation, building self-efficacy and positive outcome expectations, testing and adapting strategies to one's own health conditions, and engaging in leisure or social activities. These findings will guide future development of interventions for enhancing stroke survivors' recovery outcomes.


Cryogenic-temperature profiling of high-power superconducting lines using local and distributed optical-fiber sensors.
This contribution presents distributed and multipoint fiber-optic monitoring of cryogenic temperatures along a superconducting power transmission line down to 30 K and over 20 m distance. Multipoint measurements were conducted using fiber Bragg gratings sensors coated with two different functional overlays (epoxy and poly methyl methacrylate (PMMA)) demonstrating cryogenic operation in the range 300-4.2 K. Distributed measurements exploited optical frequency-domain reflectometry to analyze the Rayleigh scattering along two concatenated fibers with different coatings (acrylate and polyimide). The integrated system has been placed along the 20 m long cryostat of a superconducting power transmission line, which is currently being tested at the European Organization for Nuclear Research (CERN). Cool-down events from 300-30 K have been successfully measured in space and time, confirming the viability of these approaches to the monitoring of cryogenic temperatures along a superconducting transmission line.


Aminoglycoside pharmacokinetics: volume of distribution in specific adult patient subgroups.
To review the published clinical studies reporting volume of distribution for aminoglycosides in patient population subgroups. Controversies in methods used are discussed. National Library of Medicine Medlars, searched using MEDLINE. Published articles primarily relating to pharmacokinetic properties of aminoglycosides in specific adult patient subgroups published within the past 20 years were included. Pediatric studies were excluded. The methodology, assay technique, and results from clinical studies reporting aminoglycoside volume of distribution were evaluated. Clinical studies reporting aminoglycoside volume of distribution subgroups, including the methods by which their results were derived, are tabulated. The expected aminoglycoside volume of distribution can vary, depending on a patient's clinical presentation. Data presented will allow a more refined initial estimation of volumes of distribution, which may facilitate the achievement of desired aminoglycoside serum concentrations.


The effects of simulated and actual visual impairment on the Montreal Cognitive Assessment.
Many cognitive assessments include a visual component; however, adults may experience a decline in visual acuity with age. Scores on cognitive assessments of adults with visual impairments are typically lower than adults with normal vision, however, it is unclear if these lower scores are a consequence of cognitive or visual impairment. We measured the impact of simulated visual impairment on a cognitive screening measure. Undergraduate students were administered the Montreal Cognitive Assessment (MoCA) under three vision conditions (20/20, simulated 20/80, simulated 20/200). We found a main effect of vision condition on test performance such that there is a statistically significant difference between scores on the 20/20 and 20/80 conditions and 20/200. However, no differences were observed between 20/80 and 20/200. Participants' performance decreased with simulated impairments. A secondary between-subject analysis was conducted on a sample of older adults with and without vision impairment; no differences were found.


Norwegian industry and health promotion 1910-1967.
The development of occupational health services in Norway is explored by making a case study of both a chocolate factory and a cement factory. The study shows how different motives and ideological positions promoted the industrial health service. Prominent among them were a social and political philosophy, those of welfare capitalism, as an alternative to socialism and state policy in building the affluent society and the move toward improvements of production. All leading to a growing interest in the human factor in industry, where the medical officer should help to shape a satisfied, rational and productive worker in a healthy work environment.


Interferon therapy in Hodgkin's disease. A case report.
The treatment of a case of Hodgkin's disease (lymphocyte predominance, stage IV B) with exogenous i.m. interferon therapy is described. B symptoms disappeared, diseased nodes and pulmonary infiltrations decreased in size, and laboratory values normalized. Clinical improvement was associated with increased mitogenic responsiveness of the patient's lymphocytes towards various stimuli in vitro. After almost half a year's treatment tumour progression and a decreased mitogenic response were again observed. Interferon treatment was then abandoned and combined cytostatic courses were instituted. Partial remission was achieved after 6 months of cytostatic therapy, i.e. 1 year after the start of treatment.


Effects of dietary supplementing tannic acid in the ration of beef cattle on rumen fermentation, methane emission, microbial flora and nutrient digestibility.
Four adult Simmental male cattle (376 ± 9.0 kg initial BW), fitted with permanent rumen cannulas, were used in a 4 × 4 Latin square design to investigate the effects of dietary supplementing tannic acid (TA) on rumen fermentation, methane (CH4 ) production, rumen microbes, nutrient digestibility and plasma biochemical parameters. Four levels of TA, that is 0, 6.5, 13.0 or 26.0 g/kg dry matter (DM), were added to the basal ration (composed of corn silage and concentrate mixture) as experimental treatments respectively. Each experimental period consisted of a 12-day adaptation phase followed by a 3-day sampling phase. The results showed that supplementing TA at 26.0 g/kg DM decreased the relative abundance of protozoa, methanogens and Ruminococcus albus to the total ruminal bacterial 16S rDNA in beef cattle (p < 0.05). The results also showed that supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) the CH4 production (l/kg DM intake) by 11.1%, 14.7% and 33.6% respectively. Supplementing TA at 13.0 or 26.0 g/kg DM decreased the ratio of acetate to propionate and ammonia nitrogen (NH3 -N) (p < 0.05) and tended to decrease the total volatile fatty acid (VFA) concentration of rumen fluid (p = 0.07). Supplementing TA at 26.0 g/kg DM decreased DM and organic matter (OM) digestibility (p < 0.05), supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) crude protein (CP) digestibility by 5.0%, 8.6% and 15.7%, respectively, and supplementing TA at 6.5, 13.0 or 26.0 g/kg DM increased (p < 0.05) the plasma total antioxidant capability. It was concluded that supplementing TA in the ration of beef cattle decreased the CH4 production and digestibility of CP of beef cattle. Supplementing TA could be an effective option to mitigate CH4 emission form cattle, further research is necessary to study the effects of TA on the performance of cattle.


Assessment of Apparent Diffusion Coefficients and SUVs as Predicators of Histological Differentiation in Anal Squamous Cell Carcinoma.
The study aims to assess minimal apparent diffusion coefficient (ADCmin) and SUVmax as predictors of histological differentiation in patients with anal squamous cell carcinoma (ASCC) and to determine cutoff values for each histopathological tumor grade. A retrospective study of 41 ASCC patients (14 males, 27 females; mean age, 65 ± 13 years) staged with FDG PET/CT and MRI (mean scan time interval, 21 ± 11 days). SUVmax and ADCmin values were measured and compared with histopathological tumor grading obtained from biopsy. The mean size and tumor volume were 3 ± 2 cm and 16.5 ± 27.3 cm3, respectively. The mean ADCmin values for well-, moderately, and poorly differentiated ASCC were 935 ± 179, 896 ± 123, and 637 ± 114, respectively. The mean SUVmax for well-, moderately, and poorly differentiated ASCC were 6.9 ± 1.8, 11.5 ± 4.1, and 13.4 ± 2.6, respectively. The difference in mean ADCmin values between poorly and moderately/well-differentiated tumors was statistically significant, whereas this was not significant between moderately and well-differentiated tumors. Differences in SUVmax values were statistically significant between poorly/moderately and well-differentiated tumors, whereas there was no statistical significance between poorly and moderately differentiated tumors. By combining the 2 modalities using cutoff values of 675 × 10-6 mm2·s-1 for ADCmin and 8.5 for SUVmax, it was possible to differentiate the tumor categories with a sensitivity, specificity, positive predictive value, and negative predictive value, respectively, of 84.6%, 96.4%, 91.7%, and 93.1% for well-differentiated ASCC, 76.5%, 87.5%, 81.3%, and 84% for moderately, and 90.9%, 89.3%, 76.9%, and 96.2% for poorly differentiated ASCC, respectively. ADCmin and SUVmax values correlated with the degree of differentiation in ASCC and can be used as predictors of tumor grading and aggressiveness. Combined ADCmin and SUVmax cutoff values can therefore be used for early patient risk stratification and treatment decision making.


Enhancement of the caspase-independent apoptotic sensitivity of pancreatic cancer cells by DHMEQ, an NF-kappaB inhibitor.
The effects of the nuclear factor (NF)-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), combined with tumor necrosis factor (TNF)-alpha were evaluated in PK-8 pancreatic cancer cells. NF-kappaB was activated by TNF-alpha; however, the administration of DHMEQ abrogated its transcriptional activity. The addition of DHMEQ to TNF-alpha markedly induced apoptosis in PK-8 cells with down-regulation of anti-apoptotic c-FLIP and survivin. Combined treatment significantly suppressed cell viability in vitro, and the anti-tumor effect of DHMEQ was also significant in vivo. We investigated the apoptosis signaling pathway involved in these cell killing effects. Truncated Bid was produced by activated caspase-8, and the subsequent depolarization of the mitochondrial membrane potential (Delta Psi m) peaked at 6 h. Then, the activity of caspase-3 was up-regulated 8-fold. Z-VAD-fmk (a pan-caspase inhibitor) perfectly inhibited the up-regulation of caspase-3 but failed to reverse the cell viability. The above findings indicated that the growth inhibitory effect of combined treatment largely depended on mitochondria-associated caspase-independent apoptosis. The intracellular behavior of apoptosis-inducing factor (AIF) following depolarization of Delta Psi m suggested that AIF executed such a caspase-independent apoptosis. Interestingly, caspase-dependent apoptosis appeared within 6 h, whereas the caspase-independent apoptosis lagged. Thus, the addition of DHMEQ to TNF-alpha was capable of inducing caspase-independent apoptosis in pancreatic cancer cells. Once caspase-independent apoptosis was induced, the apoptosis demonstrated powerful cytotoxicity. Therefore, DHMEQ in combination with TNF-alpha may be a promising treatment for pancreatic cancer.


Trajectories of alcohol use and electrophysiological and morphological indices of brain development: distinguishing causes from consequences.
Alcoholism is a major public health problem. Patterns of drinking during adolescence can influence the likelihood of this outcome. Both environmental variation and familial/genetic susceptibility play important roles in this process. While there is some evidence to suggest that metabolic factors play a role in whether some individuals are protected from developing alcohol problems, there is substantial reason to look for cognitive factors that are associated with increased susceptibility. Developmental trajectories for information processing that can be reflected in P300 amplitude changes over time, as well as trajectories describing acquisition of postural control when compared in offspring from families with multiple cases of alcoholism or those with none or few, suggest that brain development provides a clue to why some individuals are more susceptible to becoming alcoholic. Finally, differences seen in amygdala volume between high- and low-risk adolescents suggest that functional differences seen in electrophysiological responding or neuropsychological test performance may have anatomical correlates.