Salted meat consumption and the risk of laryngeal cancer.
A hospital-based, case-control study of laryngeal cancer was conducted in the Oncology Institute, Montevideo, Uruguay, during 1988-1992, in which 143 new cases and 460 controls were interviewed. The study was restricted to males. As in most previous studies tobacco smoking and alcohol drinking were the major risk factors. Past and current salted meat consumption was associated with increased risks of laryngeal cancer, after controlling for the effects of tobacco and alcohol. Cigarette smoking and consumption of salted meat appeared to increase the risk of laryngeal cancer in a multiplicative fashion. Fresh meat consumption (beef) was also associated with an increased risk of laryngeal cancer (OR 2.0). After controlling for fresh meat ingestion, the estimates for salted meat remained significant.


Chordoma: a systematic review of the epidemiology and clinical prognostic factors predicting progression-free and overall survival.
The aim of this systematic review is to describe the epidemiology of chordoma and to provide a clear overview of clinical prognostic factors predicting progression-free and overall survival. Four databases of medical literature were searched. Separate searches were performed for each of the two objectives. Reference and citation tracking was performed. Papers were processed by two independent reviewers according to a protocol that included risk of bias analysis. Disagreement was resolved by discussion. Pooled analyses were planned if homogeneity of data would allow. Incidence-incidence rates ranged between 0.18 and 0.84 per million persons per year and varied between countries and presumably between races. On average patients were diagnosed in their late fifties and gender data indicate clear male predominance. Two of the largest studies (n = 400 and n = 544) reported different anatomical distributions: one reporting the skull base and sacrococcygeal area affected in 32% and 29% of cases, whereas the other reporting that they were affected in 26% and 45% of cases, respectively. Statistically significant adverse prognostic factors predicting progression-free and overall survival include female sex, older age, bigger tumour size, increasing extent of tumour invasion, non-total resection, presence of metastasis, local recurrence, and dedifferentiated histological subtype. Incidence rate and anatomical distribution vary between countries and presumably between races. Most chordomas arise in the skull base and sacrococcygeal spine, and the tumour shows clear male predominance. Multiple adverse prognostic factors predicting progression-free and overall survival were identified in subgroups of patients. These slides can be retrieved under Electronic Supplementary Material.


MRI in the evaluation of spina bifida patients in the remote period after meningomyelocele repair.
MRI was performed on 22 patients ranging in age from 3 months to 16 years who had closure of their meningomyelocele shortly after birth. These patients had developed new clinical findings suggestive of spinal cord dysfunction. MRI showed low placement of the spinal cord in all 22. Six patients had lipomas, five had diastematomyelia and six had hydromyelia. Four patients had an obviously dysplastic terminal cord.


Applying Dutch and US versions of the BSID-II in Dutch children born preterm leads to different outcomes.
The aim of the present study was to evaluate whether the application of Dutch versus US test procedures and norms of the Bayley Scales of Infant Development - 2nd edition (BSID-II) leads to different developmental outcomes. The BSID-II was administered to 376 preterm infants (191 males, 185 females; mean gestational age 30wks [SD 2.7], mean birth-weight 1242g [SD 385]) at corrected ages of 6, 12, 24, and/or 36 months. Raw scores were calculated twice with US and Dutch test procedures. Raw scores as well as Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores, calculated on the basis of Dutch versus US normative data, were compared. Small but statistically significant Dutch-US differences were found between raw scores. Large, clinically relevant Dutch-US differences were found for MDI and PDI scores, especially at 6 and 12 months. These differences were likely to have been caused by a bias in the Dutch normative data, although a slower developmental pace of Dutch children in general could also have a role. This study highlights the problems that can occur when using a test that was developed in another country, even when local standardization is available.


Spontaneous Isolated Celiac Artery Dissection: A Case Report.
Abdominal pain is a common chief complaint that can represent a wide breadth of diagnoses, ranging from benign to life-threatening. As our diagnostic tools become more sophisticated, we are able to better identify more causes of potentially life-threatening diseases. One such disease that is relatively unfamiliar to clinicians is spontaneous isolated celiac artery dissection (SICAD). We describe a case of a 46-year-old man who presented to our emergency department with a chief complaint of abdominal pain and was found to have a SICAD and was successfully treated with anticoagulation, antihypertensives, and observation. It is important for emergency physicians to keep this potentially life-threatening condition in mind and to know the appropriate first steps once identified.


A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides.
Depletion of a subset of 70K stress proteins in yeast mutants shows that they are involved in the post-translational import of precursor polypeptides into both mitochondria and the lumen of the endoplasmic reticulum. The identification of such a basic function may explain the remarkable evolutionary conservation of the gene family encoding these proteins.


The percutaneous electrocoagulation vasectomy technique--a comparative trial with the standard incision technique at Marie Stopes House, London.
One-hundred-and-one men requesting vasectomy in 1985 for the purpose of limiting family size were admitted to a study of standard incision and monopolar diathermy, and a new percutaneous electrocoagulation vasectomy procedure. Semen specimens were tested at 10 and 12 weeks after surgery. Men were telephoned at 2, 12 and 24 weeks post-surgery to elicit complications and complaints. Half of the men having the standard incision procedure and about one-third of the men undergoing the percutaneous procedure complained of discomfort during the surgery. At the two-week telephone contact, 23% of those having the standard incision and 66% of those having the percutaneous procedure reported complications. There were few complications or complaints reported at the long-term follow-up contacts with either method; although twice as many men in the percutaneous group were not declared sterile by the end of the study period. Failure rates were 2.0% for the standard incision procedure and 7.8% for the percutaneous approach.


Multicentre retrospective study on endoscopic ultrasound complications.
Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures. By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience. Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe. Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.


Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs.
To estimate the current and future economic burdens of Type 1 and Type 2 diabetes in the UK. A top-down approach was used to estimate costs for 2010/2011 from aggregated data sets and literature. Prevalence and population data were used to project costs for 2035/2036. Direct health costs were estimated from data on diagnosis, lifestyle interventions, ongoing treatment and management, and complications. Indirect costs were estimated from data on mortality, sickness, presenteeism (potential loss of productivity among people who remain in work) and informal care. Diabetes cost approximately £ 23.7bn in the UK in 2010/2011: £ 9.8bn in direct costs (£1bn for Type 1 diabetes and £ 8.8bn for Type 2 diabetes) and £ 13.9bn in indirect costs (£ 0.9bn and £ 13bn). In real terms, the 2035/2036 cost is estimated at £ 39.8bn: £ 16.9bn in direct costs (£ 1.8bn for Type 1 diabetes and £ 15.1bn for Type 2 diabetes) and £ 22.9bn in indirect costs (£ 2.4bn and £ 20.5bn). Sensitivity analysis applied to the direct costs produced a range of costs: between £ 7.9bn and £ 11.7bn in 2010/2011 and between £ 13.8bn and £20bn in 2035/2036. Diabetes currently accounts for approximately 10% of the total health resource expenditure and is projected to account for around 17% in 2035/2036. Type 1 and Type 2 diabetes are prominent diseases in the UK and are a significant economic burden. Data differentiating between the costs of Type 1 and Type 2 diabetes are sparse. Complications related to the diseases account for a substantial proportion of the direct health costs. As prevalence increases, the cost of treating complications will grow if current care regimes are maintained.


Anastomotic stenosis of the descending colon caused by barium granuloma formation following barium peritonitis: report of a case.
Anastomotic stricture reportedly often recurs following barium peritonitis, regardless of whether the anastomotic diameter is initially sufficient. However, the causes of repetitive stricture have not been clarified. We report a case that suggests the pathophysiology of recurrent anastomotic strictures following barium peritonitis. The patient was a 39-year-old Japanese man with idiopathic perforation of the descending colon after undergoing an upper gastrointestinal barium contrast study. After emergency peritoneal lavage and diverting colostomy, created using the perforated region, the patient recovered uneventfully and 3 months later, the colostomy was closed and the perforated colon was resected. However, 7 months after colostomy closure, abdominal distention gradually developed, and colonoscopy revealed an anastomotic stricture. The patient was referred to our hospital where he underwent resection of the anastomotic stricture. The surgical specimen exhibited barium granulomas not only in the subserosa of the entire specimen, but also in the submucosa and lamina propria localized in the anastomotic site. These findings suggest that barium was embedded in the submucosa and lamina propria with manipulation of the stapled anastomosis and that the barium trapped in the anastomotic site caused persistent inflammation, resulting in an anastomotic stricture.


Genetic damage induced by CrO3 can be reduced by low doses of Protoporphyrin-IX in somatic cells of Drosophila melanogaster.
Several epidemiological studies have reported the relation between chromium exposure (used in different industrial processes) and cancer risk. Evidence indicates that the hexavalent form is mutagenic and carcinogenic. Chemoprevention has emerged as a good strategy for reducing the risk from exposure to heavy metals. There is evidence that some tetrapyrrols such as protoporphyrin IX (PP-IX), a porphyrin without a metal center and which is a precursor of hemoglobin and cytochrome, acts as an antioxidant modulating the induction of antioxidant enzymes. The present study was performed to evaluate their antimutagenic potential of PP-IX against genetic damage induced by chromium trioxide (CrO3). The wing spot test was used. Groups of 48 h-old larvae were pretreated for 24 h with 0, 0.69, 6.9, or 69 mM of PP-IX, after which groups of larvae were fed 0.025-2.5 mM CrO3 solution in Drosophila instant medium. The results indicated that the lower PP-IX concentration (0.69 mM) significantly reduced the genetic damage induced by all CrO3 concentrations tested. In contrast, 6.9 and 69 mM only inhibited the damage induced by CrO3 2.5 mM. Absence of an inhibitor effect of PP-IX against 20 Gy gamma rays suggested that this porphyrin acted primarily by forming complexes with chromium at low doses, inactivating its genotoxic action rather than capturing or inactivating the reactive oxygen species generated by the chromium.


Increase in contralateral prophylactic mastectomy conversation online unrelated to decision-making.
The increased uptake of contralateral prophylactic mastectomy (CPM) among breast cancer patients remains poorly understood. We hypothesized that the increased rate of CPM is represented in conversations on an online breast cancer community and may contribute to patients choosing this operation. We downloaded 328,763 posts and their dates of creation from an online breast cancer community from August 1, 2000, to May 22, 2016. We then performed a keyword search to identify posts which mentioned breast cancer surgeries: contralateral prophylactic mastectomy (n = 7095), mastectomy (n = 10,889), and lumpectomy (n = 9694). We graphed the percentage of CPM-related, lumpectomy-related, and mastectomy-related conversations over time. We also graphed the frequency of posts which mentioned multiple operations over time. Finally, we performed a qualitative study to identify factors influencing the observed trends. Surgically related posts (e.g., mentioning at least one operation) made up a small percentage (n = 27,678; 8.4%) of all posts on this community. The percentage of surgically related posts mentioning CPM was found to increase over time, whereas the percentage of surgically related posts mentioning mastectomy decreased over time. Among posts that mentioned more than one operation, mastectomy and lumpectomy were the procedures most commonly mentioned together, followed by mastectomy and CPM. There was no change over time in the frequency of posts that mentioned more than one operation. Our qualitative review found that most posts mentioning a single operation were unrelated to surgical decision-making; rather the operation was mentioned only in the context of the patient's cancer history. Conversely, the most posts mentioning multiple operations centered around the patients' surgical decision-making process. CPM-related conversation is increasing on this online breast cancer community, whereas mastectomy-related conversation is decreasing. These results appear to be primarily informed by patients reporting the types of operations they have undergone, and thus appear to correspond to the known increased uptake of CPM.


Changes in utilization and costs for patients with rheumatoid arthritis, 1997 to 2006.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that often results in joint pain, inflammation and bone erosions. Perhaps the most notable change in RA treatment during the last decade is the advent of biologics, and, in particular, anti-tumour necrosis factor agents. Given these advances, it is useful to assess how healthcare and work-loss costs of patients with RA have changed. Our objective was to assess changes in healthcare utilization and costs from 1997 to 2006 for patients diagnosed with RA. Two cohorts (1997 and 2006) of patients with RA and matched controls were identified from two administrative claims databases along with subsamples of employed patients and matched controls. The analysis focused on the more homogeneous employee subsample. We compared annual excess co-morbidity rates, resource utilization and healthcare and work-loss costs per patient between the 1997 (n = 279) and 2006 cohorts (n = 837) with difference-in-differences methodology. Results with p < 0.05 were considered statistically significant. In the employee subsample, there were no statistically significant differences in the excess prevalence of non-RA co-morbidities or Charlson Co-morbidity Index results, except for cardiovascular disease, which decreased by 11.1%. Excess number of ED visits and days hospitalized decreased by 1.1 visits/patient and 0.9 days/patient, respectively, while rheumatologist visits increased by 0.9 visits/patient. Excess per-patient direct costs were unchanged. However, drug costs increased by $US633/patient, but medical costs decreased by $US618/patient (not significant) [year 2006 values]. For employed patients with RA, there were significant reductions in per-patient excess hospital days, as well as ED visits, and no changes in excess total direct costs over time. New treatments introduced during the study period may be associated with cost savings that offset changes in employee utilization of drug and medical services. In addition, the reductions in excess ED visits and hospital days suggest improvements in patient quality of life.


Reducing age-related Memory Deficits: The Roles of Environmental Support and self-initiated Processing Activities.
The notion that memory performance in older adults can be boosted by information provided by the environment was proposed by Craik (1983). The suggestion was that age-related memory deficits can be attenuated and sometimes even eliminated by a complementary combination of environmental support and consciously controlled self-initiated activities. The objective of the present article was to review the subsequent empirical and theoretical work on the topics of environmental support and self-initiated ativities as they relate to the effects of aging on human memory. The notion of schematic support from the person's knowledge base is introduced and its relevance discussed. In addition, the effects of various types of support on encoding and retrieval processes in older adults are desribed, and the increasing theoretical importance of executive processes in reducing age-related memory deficits is discussed. As one main conclusion, it is suggested that self-initiated control processes interact with both information provided by the environment and by the person's knowledge base to improve the effectiveness of encoding and retrieval processing in older adults.


[Breast augmentation by implants: a review of surgical practices. A study among French plastic surgeons].
In the framework of the 2005 report on mammary implants prepared by the Société française de chirurgie plastique reconstructrice et esthétique (SOF.CPRE), we conducted a survey among french plastic surgeons involved in the field. We elaborated a questionnaire that we distributed twice to the 600 members of the society; a total of 261 responded. Analysis of the data collected provides information on the socioprofessional characteristics of the responding surgeons, and on the devices, products and techniques they use. Finally, the survey has permitted to identify their qualitative perception of breast implant products currently available. Ranking these items by order of frequency provides a snapshot of the current procedures and practices in use for breast augmentation surgery in France.


Effectiveness of Cognitive Functional Therapy Versus Core Exercises and Manual Therapy in Patients with Chronic Low Back Pain after Spinal Surgery: Randomized Controlled Trial.
Our aim was to investigate whether cognitive functional therapy (CFT) was more effective than core exercises and manual therapy in improving pain and function for patients with chronic low back pain after spinal surgery. This study was a randomized controlled superiority trial in a university hospital and a private physical therapy clinic in Santa Catarina, Brazil. Eighty participants who were 18 to 75 years old and had chronic low back pain after spinal surgery received 4 to 12 treatment sessions of CFT or core exercises and manual therapy once per week for a maximum period of 12 weeks. Primary outcomes were pain intensity (numeric pain rating scale, scored from 0 to 10) and function (Patient-Specific Functional Scale, scored from 0 to 10) after intervention. We obtained primary outcome data for 75 participants (93.7%). CFT was more effective, with a large effect size, than core exercises and manual therapy in reducing pain intensity (mean difference [MD] = 2.42; 95% CI = 1.69 to 3.14; effect size [d] = 0.85) and improving function (MD = -2.47; 95% CI = -3.08 to -1.87; effect size = 0.95) after intervention (mean = 10.4 weeks [SD = 2.17] after the beginning of treatment). The differences were maintained at 22 weeks for pain intensity (MD = 1.64; 95% CI = 0.98 to 2.3; effect size = 0.68) and function (MD = -2.01; 95% CI = -2.6 to -1.41; effect size = 0.81). CFT was more effective than core exercises and manual therapy, with large effect sizes, and may be an option for patients with chronic low back pain after spinal surgery. CFT reduces pain and improves function, with large effect sizes, compared with core exercises and manual therapy. The difference between CFT and core exercises and manual therapy was sustained at the midterm follow-up. Treatment with CFT may be an option for patients with chronic low back pain after spinal surgery.


Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia.
In 20 women with menorrhagia (greater than 80 ml blood loss per menstrual period) a levonorgestrel-releasing intrauterine device (Lng-IUCD) was inserted. Menstrual blood loss (MBL) was measured in two consecutive cycles before the device was inserted and after 3, 6 and 12 months of use. MBL was significantly reduced after 3 months (86%) and after 12 months the reduction was 97%. There was a significant increase (P less than 0.001) in serum ferritin during the first year of Lng-IUCD use. The Lng-IUCD seems to be an important alternative to oral medication and to hysterectomy in the treatment of menorrhagia.


Big Brain Data Initiatives in Universiti Sains Malaysia: Data Stewardship to Data Repository and Data Sharing.
The sharing of open-access neuroimaging data has increased significantly during the last few years. Sharing neuroimaging data is crucial to accelerating scientific advancement, particularly in the field of neuroscience. A number of big initiatives that will increase the amount of available neuroimaging data are currently in development. The Big Brain Data Initiative project was started by Universiti Sains Malaysia as the first neuroimaging data repository platform in Malaysia for the purpose of data sharing. In order to ensure that the neuroimaging data in this project is accessible, usable, and secure, as well as to offer users high-quality data that can be consistently accessed, we first came up with good data stewardship practices. Then, we developed MyneuroDB, an online repository database system for data sharing purposes. Here, we describe the Big Brain Data Initiative and MyneuroDB, a data repository that provides the ability to openly share neuroimaging data, currently including magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG), following the FAIR principles for data sharing.


The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.
KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.


A mechanistic approach for toxicity and risk assessment of heavy metals, hydroquinone and microorganisms in cosmetic creams.
The demand and importance of fairness creams as a major cosmetic have increased significantly in recent years. However, some of these cosmetics contain heavy metals, hydroquinone and microorganism that can cause various health problems. Therefore, the aim of this study is to determine and examine the concentration of metals (i.e. Cd, Pb, Cr, Ni, Zn, Hg), hydroquinone and microorganisms in nine different fairness creams produced by local and international brands. The health risk assessment of the tested substances for consumers was accessed through systemic exposure dosage (SED), margin of safety (MoS), lifetime cancer risk (LCR), hazard quotient (HQ) and hazard index (HI). The concentration of Zn and Hg were found the highest and measured in the range of 17.82-138.06 mg.kg-1 and 2.3-141 mg.kg-1, respectively. The concentrations of other metals were determined as 0.06-0.67 mg.kg-1 of Cd, 0.43-1.55 mg.kg-1 of Cr, 0.14-1.43 mg.kg-1 of Ni and 0.3-1.34 mg.kg-1 of Pb. HPLC results showed a significant presence of hydroquinone in the range of 0.12-7.2%. The total viable counts of cosmetic samples showed the substantial presence of microorganisms, and 44% of the collected samples surpassed the permissible limit of 100 cfu/g recommended by European Union. Many of the collected samples exceeded the MoS, HQ and HI tolerance limits. However, the LCR value in all samples was significantly higher than the acceptable limit. Therefore, it is advised to avoid overuse of these products in order to ensure human safety and reduce the risks to skin health.


Effects of low carbohydrate diets on energy and nitrogen balance and body composition in rats depend on dietary protein-to-energy ratio.
Truly ketogenic rodent diets are low in carbohydrates but also low in protein. The aim of this study was to differentiate effects of ketosis, low carbohydrate (LC) and/or low-protein intake on energy and nitrogen metabolism. We studied the nitrogen balance of rats fed LC diets with varying protein contents: LC diets consisted of 75/10, 65/20 and 55/30 percent of fat to protein (dry matter), respectively, and were iso-energetically pair-fed to a control (chow) diet to 12-wk-old male Wistar rats (n = 6 per diet). Previous studies demonstrated only LC75/10 was truly ketogenic. Food, fecal, and urine samples, as well as carcasses were collected and analyzed for heat of combustion and nitrogen (Kjeldahl method). Blood samples were analyzed for plasma protein, albumin, and triacylglycerol. All LC groups displayed less body weight gain, and the degree of reduction was inversely related to digestible crude protein intake (daily weight gain compared with chow: LC75/10: -50%; LC55/30: -20%). Nitrogen excretion by urine was related to digestible protein intake (chow: 0.23 ± 0.02 g nitrogen/d; LC75/10: 0.05 ± 0.01 g nitrogen/d). Renal energy excretion was closely associated with intake of digestible crude protein (r = 0.697) and renal nitrogen excretion (r = 0.769). Energy-to-nitrogen ratio in urine was nearly doubled with LC75/10 compared with all other groups. Total body protein was highest with chow and lowest with LC75/10. Rats fed with LC75/10 displayed features of protein deficiency (reduced growth and nitrogen balance, hypoproteinemia, depletion of body protein, and increased body and liver fat), whereas the effects with the non-ketogenic diets LC65/20 and LC55/30 were less pronounced. These results suggest that truly ketogenic LC diets in growing rats are LC diets that are also deficient in protein for growth.


Identification of an in vivo CD4+ T cell-mediated response to polymorphic membrane proteins of Chlamydia pneumoniae during experimental infection.
Chlamydia pneumoniae is an obligate intracellular bacterium that causes upper and lower respiratory tract infection in humans. C. pneumoniae harbors the polymorphic membrane protein (Pmp) family with 21 different proteins with a molecular mass around 100 kDa. The Pmps are species-specific, abundant and, together with major outer membrane protein and outer membrane protein 2, the dominant proteins in the C. pneumoniae outer membrane complex. Nevertheless, it is unknown whether Pmps are recognized by the cell-mediated immune response. To address this issue, C57BL/6J mice were infected intranasally with C. pneumoniae and the immune response to primary infection was investigated. We demonstrate, as expected, that the primary response is of the Th1 type by IgG2a- and IgG1-specific sELISA (Medac) on serum. In vivo-primed spleen lymphocytes were found to be reactive to Pmp8, Pmp20 and Pmp21 in an interferon-gamma ELISpot assay. The responses were shown to be mediated by CD4(+) T cells. To our knowledge, this is the first identification of antigens recognized by CD4(+) T cells during murine C. pneumoniae infection.


Anatomical variations in the sensory innervation of the dorsal surface of the first digit space, a cadaveric study with clinical consequences.
Radial nerve palsy is a classical complication of a humeral shaft fracture. In clinical practice, motor palsy of the radial nerve is sometimes observed without an abnormality felt in the sensory territory. We hypothesised that this dissociation between sensory and motor involvement is related to anatomical variations of the sensory innervation of the dorsal surface of the first digit space, thus, we decided to study the nature and frequency of these variations. A cadaveric study was conducted on 24 upper limbs to analyse the truncal origin of the sensory branches innervating the dorsal surface of the first digit space. The sensory branch of the radial nerve (SBRN) participated in the innervation of the dorsal surface of the first digit space in 22 limbs, an anatomical variation was present in 2 cases with a mixed innervation by the SBRN and the lateral cutaneous nerve of forearm (LCNF) in 1 case and singular innervation by LCNF, with no SBRN involvement, in 1 case. Communications between SBRN and LCNF were found in 7 cases. Pure motor radial damage, without a sensory deficit of the dorsal surface of the first digit space, does not preclude a complete traumatic injury of the radial nerve. The sensory innervation of this region can be relayed by a branch of the LCNF. IV; cadaveric study.


The response of gastric inhibitory polypeptide (GIP) and insulin to glucose in duodenal ulcer patients.
The response of Gastric Inhibitory Polypeptide (GIP) and insulin to a 50 g oral glucose tolerance test (OGTT) and an intravenous glucose infusion (IVGI), which copied the changes in plasma glucose concentrations during the OGTT, were measured in 10 patients with duodenal ulcer and in 10 healthy control subjects. The mean responses of GIP and insulin to OGTT were significantly increased in the ulcer patients. During IVGI the responses were normal. The degree of increased GIP response in the patients was positively correlated with the plasma glucose increase during the OGTT. It is postulated that the increased GIP secretion is related to a faster glucose absorption due to rapid gastric emptying in duodenal ulcer patients. No correlation was found between basal and peak gastric acid output and the GIP response in the patients. The data demonstrate that GIP secretion is not defective in duodenal ulcer patients.


Lack of Prognostic Impact of Adjuvant Radiation on Oncologic Outcomes in Elderly Women with Breast Cancer.
Radiotherapy plays an important role as adjuvant treatment in locally advanced breast cancer and in those patients who have undergone breast-conserving surgery. This study aimed to investigate the prognostic impact of adjuvant radiation on oncologic outcomes in elderly women with breast cancer. In this retrospective study, we reviewed and analyzed the characteristics, treatment outcome and survival of elderly women (aged ≥ 60 years) with breast cancer who were treated and followed-up between 1993 and 2014. The median follow up for the surviving patients was 38 (range 3-207) months. One hundred and seventy-eight patients with a median age of 74 (range 60-95) years were enrolled in the study. Of the total, 60 patients received postoperative adjuvant radiation (radiation group) and the remaining 118 did not (control group). Patients in the radiation group were significantly younger than those in the control group (P value=0.004). In addition, patients in radiation group had higher node stage (P value<0.001) and disease stage (P=0.003) and tended to have higher tumor grade (P=0.031) and received more frequent (P value <0.001) adjuvant and neoadjuvant chemotherapy compared to those in the control group. There was no statistically significant difference between two groups regarding the local control, disease-free survival and overall survival rates. In this study, we did not find a prognostic impact for adjuvant radiation on oncologic outcomes in elderly women with breast cancer.


Enantioselective synthesis of tatanans A-C and reinvestigation of their glucokinase-activating properties.
The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A-C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.


Immune checkpoint inhibitor use in antisynthetase syndrome.
We report on the unique case of a patient with antisynthetase syndrome and metastatic non-small cell lung cancer undergoing therapy with the PD-1 checkpoint inhibitor, nivolumab. Despite adequate autoimmune disease control over a period of 12 months, the patient rapidly experienced a flare of interstitial lung disease following initial nivolumab administration, which ultimately proved fatal. The use of immune checkpoint inhibitors in patients with autoimmune disease is becoming more commonplace, however this is the first reported case of the use of these agents in a patient with antisynthetase syndrome. Additionally, the patient's initial clinical presentation with antisynthetase syndrome and simultaneous primary lung cancer, a rare association of which there are few case reports, makes this case interesting and unusual.


Undescribed steroidal alkaloids from the bulbs of Fritillaria sinica.
Eight undescribed steroidal alkaloid derivatives, including three cevanine-type isosteroidal alkaloids (two N-oxide glycosides and one D-ring aromatization) (1-3), one verazine-type steroidal alkaloid derivative (4), three solanidine-type steroidal alkaloid glycosides (5-7), and one veratramine-type analogue (8), along with three known compounds (9-11) were isolated from the bulbs of Fritillaria sinica. Their structures were elucidated by comprehensive analysis of spectroscopic data, acidic hydrolysis, and X-ray crystal diffractions. In the in vitro bioassay, the anti-cancer effect, anti-oxidation and anti-inflammatory activities for the isolates were evaluated at a concentration of 10 μM.


Barriers to conducting clinical research in reproductive medicine around the world.
We asked seven senior and accomplished investigators from around the world to share their experiences conducting research in reproductive medicine.


Altered cerebral glucose metabolism in a family with clinical features resembling mitochondrial neurogastrointestinal encephalomyopathy syndrome in association with multiple mitochondrial DNA deletions.
To determine the involvement of cerebral metabolism in 2 siblings with mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE)-like disease with multiple mitochondrial DNA (mtDNA) deletions. Case report. Department of Neurology at a university medical center. Two siblings with MNGIE-like disease with multiple mtDNA deletions. Clinical, biochemical, genetic, and imaging findings, including cerebral magnetic resonance imaging, proton magnetic resonance spectroscopy, and positron emission tomography with fluorine 18-labeled deoxyglucose (FDG-PET). Genetic analysis of muscle DNA revealed multiple mtDNA deletions, while no mutations were detected in ECGF1, POLG1, ANT1, or Twinkle. Cerebral magnetic resonance imaging and proton magnetic resonance spectroscopy findings were unremarkable. Reduced regional glucose metabolism was found in a patchy and asymmetrical pattern predominantly in the frontotemporal region in both siblings by means of FDG-PET. The discrepancy between absence of clinical signs of cerebral involvement and the substantial impairment of glucose metabolism reflects a chronic subclinical encephalopathy. To our knowledge, the predominantly frontotemporal distribution has not been described previously in mitochondrial disorders.


Size-based ecological interactions drive food web responses to climate warming.
Predicting climate change impacts on animal communities requires knowledge of how physiological effects are mediated by ecological interactions. Food-dependent growth and within-species size variation depend on temperature and affect community dynamics through feedbacks between individual performance and population size structure. Still, we know little about how warming affects these feedbacks. Using a dynamic stage-structured biomass model with food-, size- and temperature-dependent life history processes, we analyse how temperature affects coexistence, stability and size structure in a tri-trophic food chain, and find that warming effects on community stability depend on ecological interactions. Predator biomass densities generally decline with warming - gradually or through collapses - depending on which consumer life stage predators feed on. Collapses occur when warming induces alternative stable states via Allee effects. This suggests that predator persistence in warmer climates may be lower than previously acknowledged and that effects of warming on food web stability largely depend on species interactions.


Determination of mutation trend in hemagglutinins by means of translation probability between RNA codons and mutated amino acids.
In this study, we used the 183 translation probabilities between RNA codons and mutated amino acids to construct the theoretical distributions of mutated amino acids in hemagglutinins of influenza A virus. We then compared the actual distributions of mutated amino acids from 953 hemagglutinins with their theoretical ones. The results demonstrated that mutated amino acids generally follow the direction of the theoretical distributions governed by RNA codons. This, in turn, highlights the mutation trend of amino acids in hemagglutinins and provides a method for estimating possible mutations in a protein according to its theoretical distributions of mutated amino acids.


Design, synthesis and biological evaluation of novel indole-piperazine derivatives as antibacterial agents.
Herein, a series of novel indole-piperazine derivatives were synthesized. Bioassay results showed the title compounds exhibited moderate to good bacteriostatic efficacy against the test Gram-positive bacteria and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Among theses compounds, three remarkable compounds 8f, 9a, and 9h exhibited superior in vitro antibacterial profiles for anti- S. aureus and anti-MRSA to that of gentamicin. Hit compound 9a manifested a rapid bactericidal kinetic effect on MRSA, with no resistance observed after 19 days of sequential passaging. And 8 µg/mL of compound 9a displayed considerable post antibacterial effects to that of ciprofloxacin at the concentration of 2 µg/mL. Cytotoxic and ADMET studies indicated, to some extent, compounds 8f, 9a, and 9h were up to the standard for antibacterial drugs. These results suggest that indole/piperazine derivatives based on the title compounds can serve as a new scaffold for antimicrobial development.


Comparison of suicide attempts among nationally representative samples of Mexican adolescents 12 months before and after the outbreak of the Covid-19 pandemic.
There is serious concern over the increase in mental health problems during the coronavirus disease 2019 (Covid-19) pandemic. Based on data from two Mexican National Health and Nutrition Surveys conducted in 2018-2019 and 2020 (n = 17,925 and 4,913, respectively), we estimated the prevalence of suicide attempts among adolescents 10-19 years old in the previous year. We constructed a multivariate logistic regression model adjusted by sociodemographic characteristics and contextual variables for the Covid-19 pandemic. The prevalence of suicide attempts in the previous year was similar in both surveys. We found that women, youth in urban localities and individuals living in households where a family member had lost her/his job as a result of the Covid-19 contingency were more likely to attempt suicide compared to their counterparts. On the other hand, attending classes online proved to be a protective factor (aOR=0.3, 95% CI=0.1, 0.8, p = 0.022). The principal limitation of our study concerned the restricted size of our sample for the 2020 survey wave. Population-level policies aimed at providing economic protection and helping youth to return to school would exert a favorable impact on the mental health and suicidal behavior of youths.


Characterization of the glyceraldehyde-3-phosphate dehydrogenase gene family from Kluyveromyces marxianus--polymerase chain reaction-single-strand conformation polymorphism as a tool for the study of multigenic families.
Three glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes from Kluyveromyces marxianus were identified and characterized. The coding region of two of them (GAP2 and GAP3) is very similar (99.6% homology). The other gene (GAP1) is only 86% homologous to GAP2 or GAP3 and is responsible for the expression of Gap1p. This protein is extremely homologous to the K. marxianus cell wall protein p37, presumably involved in flocculation. However, no leader sequence could be detected in this gene. The identification of the three genes was possible with the use of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), as it permits us to overcome the difficulties caused by the high homology amongst the genes. Expression of the GAPDH genes under different carbon sources (glucose or ethanol) was assessed either by Northern blot or reverse transcription-PCR-SSCP analysis, revealing that genes GAP1 and GAP2, but not GAP3, are transcribed. The results also indicate that the transcription of the gene encoding the cell wall protein p37 (Gap1p) is not dependent on the carbon source, in contrast with the expression of the gene GAP2, which is affected in cells growing in a glucose-depleted medium.


Progesterone metabolites regulate induction, growth, and suppression of estrogen- and progesterone receptor-negative human breast cell tumors.
Of the nearly 1.4 million new cases of breast cancer diagnosed each year, a large proportion is characterized as hormone receptor negative, lacking estrogen receptors (ER) and/or progesterone receptors (PR). Patients with receptor-negative tumors do not respond to current steroid hormone-based therapies and generally have significantly higher risk of recurrence and mortality compared with patients with tumors that are ER- and/or PR-positive. Previous in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines. Here in vivo studies were conducted to investigate the ability of 5αP and 3αHP to control initiation, growth, and regression of ER/PR-negative human breast cell tumors. ER/PR-negative human breast cells (MDA-MB-231) were implanted into mammary fat pads of immunosuppressed mice, and the effects of 5αP and 3αHP treatments on tumor initiation, growth, suppression/regression, and histopathology were assessed in five separate experiments. Specific radioimmunoassays and gas chromatography-mass spectrometry were used to measure 5αP, 3αHP, and progesterone in mouse serum and tumors. Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP. When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa. Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors. The levels of 5αP in tumors, regardless of treatment, were about 10-fold higher than the levels of 3αHP, and the 5αP:3αHP ratios were about fivefold higher than in serum, indicating significant changes in endogenous synthesis of these hormones in tumorous breast tissues. The studies showed that estrogen/progesterone-insensitive breast tumors are sensitive to, and controlled by, the progesterone metabolites 5αP and 3αHP. Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions. The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress. The results provide the first hormonal theory to explain tumorigenesis of ER/PR-negative breast tissues and support the hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions. The findings suggest new diagnostics based on the relative levels of these hormones and new approaches to prevention and treatment of breast cancers based on regulating the levels and action mechanisms of anti- and pro-cancer progesterone metabolites.


Electron probe microanalysis of the subcellular compartments of bovine adrenal chromaffin cells. Comparison of chromaffin granules in situ and in vitro.
The elemental and water content of cultured bovine adrenal chromaffin cells and their secretory chromaffin granules have been measured and compared with isolated chromaffin granules using quick freezing, ultracryomicrotomy, and electron microprobe analysis methods. In units of millimole/kilogram dry weight (+/- S.E.) granules in situ contained: P, 523 +/- 32; K+, 124 +/- 9; S, 82 +/- 3; Cl-, 74 +/- 9; Ca2+, 13 +/- 2; Mg2+, 6 +/- 2; and Na+, -2 +/- 2. Following routine isolation in isotonic sucrose buffer, granule K and Cl- had decreased while granule Na+ increased. Cl- exhibited a consistent decrease to 35-40 mmol/kg dry weight. Granule Na+ and K+ concentrations ranged from 43 to 12 mmol/kg and 28 to 60 mmol/kg dry weight, respectively, depending on the Na+ and K+ content of the buffer. Despite the redistribution of monovalent ions, granule Ca2+, granule P, being in the form of ATP, and granule S, being in the form of protein, were not significantly changed. The stability of these elements is consistent with the existence of a stable storage complex for Ca2+, ATP, and protein. Using the granule as an internal standard with a water content of 66%, the water contents of external space, nucleus, cytoplasm, and mitochondria were estimated to be 89, 88, 82, and 70%, respectively. Wet weight concentrations for each element were calculated for granules and cytoplasm from which the transgranular concentration gradients for K+, Cl-, and Na+ were determined. Cl-, a permeant anion, was 2-fold higher in the granule than in the cytoplasm while K+, a slightly permeant cation, had an opposite distribution ratio slightly less than two. Together, the K+ and Cl- data suggest the presence of an inside-positive granule membrane potential of approximately 10-16 mV. The surprising lack of Na+ from the granule matrix suggests a hugh inward gradient for Na+ even though the Na+ content of chromaffin cell cytoplasm is low at 5 mmol/kg water. The lack of an outward Na+ gradient is important in that it indicates that the previously described electroneutral Na+-Ca2+ exchange system, by which isolated granules accumulate Ca2+, does not operate in mature granules in situ. Consequently, if chromaffin granules regulate internal calcium during stimulus secretion coupling, a mechanism other that Na+-Ca2+ exchange is necessary.


Controlling the electrochemically active area of carbon fiber microelectrodes by the electrodeposition and selective removal of an insulating photoresist.
A new and simple method permits control of the electrochemically active area of a carbon fiber microelectrode. An electrophoretic photoresist insulates the 10-microm-diameter carbon fiber microelectrodes. Photolysis of the photoresist followed by immersion of the exposed area into a developing solution reveals electroactive carbon fiber surface. The electroactive surface area exposed can be controlled with a good degree of reproducibility.


Successful cryoablation of an incessant atrial tachycardia arising from the right atrial appendage.
The right atrial appendage can be the origin of focal atrial tachycardias. Their ablation can be challenging owing to the complexity of the appendage anatomy. To our knowledge, we describe the first successful solid tip cryoablation of a focal tachycardia within the right atrial appendage in a patient presenting with tachycardia-induced cardiomyopathy.


Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells.
The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis. Furthermore, Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally, Gclc deficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. Our results thus suggest that Gclc is required to ensure the development of MZB, the mitochondrial ETC integrity in FoB, and the efficacy of antiviral humoral immunity.


Wavelet transform analysis of heart rate variability during myocardial ischaemia.
Analysis of heart rate variability (HRV) is a valuable, non-invasive method for quantifying autonomic cardiac control in humans. Frequency-domain analysis of HRV involving myocardial ischaemic episodes should take into account its non-stationary behaviour. The wavelet transform is an alternative tool for the analysis of non-stationary signals. Fourteen patients have been analysed, ranging from 40 to 64 years old and selected from the European Electrocardiographic ST-T Database (ESDB). These records contain 33 ST episodes, according to the notation of the ESDB, with durations of between 40s and 12 min. A method for analysing HRV signals using the wavelet transform was applied to obtain a time-scale representation for very low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm. The design and implementation using fast algorithms included a specially adapted decomposition quadrature mirror filter bank for the frequency bands of interest. Comparing a normality zone against the ischaemic episode in the same record, increases in LF (0.0112 +/- 0.0101 against 0.0175 +/- 0.0208 s2 Hz(-1); p<0.1) and HF (0.0011 +/- 0.0008 against 0.00 17 +/- 0.0020 s2 Hz(-1); p<0.05) were obtained. The possibility of using these indexes to develop an ischaemic-episode classifier was also tested. Results suggest that wavelet analysis provides useful information for the assessment of dynamic changes and patterns of HRV during myocardial ischaemia.


Anticonvulsant activity of reaction products of 5,5-diphenylhydantoin with substituted methylene bromides.
Some derivatives of 5,5-diphenylhydantoin (phenytoin) were synthesized by the alkylation of phenytoin with substituted methylene bromides. The hydantoins were evaluated for possible anticonvulsant activity in the maximal electroshock (MES)- and subcutaneous pentylenetetrazole (ScMet)-induced seizures and for neurotoxicity in the rotorod test in mice and rats.


Dentin surface roughness vs. bond strength of dentin adhesives.
The effects of differently prepared dentin surfaces on the bond strength mediated by five dentin adhesive/composite resin systems were investigated: Clearfil new bond/Clearfil Ray, Gluma/Lumifor, Scotchbond/Silux, Scotchbond 2/Valux, and Tenure/Silux. Bonding surfaces were produced either by wet-grinding of human teeth on SiC paper, grits 180, 240, 320, 400, 600, and 4000, respectively, or by cutting them with dental preparation instruments. The surfaces of the dentin were analyzed by a profilometer. Tensile bond strengths (TBS) were determined two min after light activation of the restorative systems. In spite of greatly different effective areas for bonding, ANOVA showed no significant differences on the 5% level between the TBS means of one material system recorded for the different dentin preparations. It was concluded that the dentin roughness produced by preparation has no significant influence on early bond strengths of bonding composite resin systems.


Effects of various cephalosporins on the proximal tubule of the human kidney.
Cephamandol 6.0 g, cephazolin 6.0 g or cephacetrile or cephalothin 8.0 g were administered as short-term infusions on 3 consecutive days to informed volunteers, who had no history or evidence of impairment of renal function. There were 15 subjects in the cephamandol, cephacetrile and cephalothin groups and 14 subjects in the cephazolin group. Alanine-aminopeptidase, a characteristic tubule enzyme, was determined in a 24-hour urine 2 days before administration, during the 3 day administration and on the 4 subsequent days. In addition, alanine-aminopeptidase was also estimated immunologically in concentrated urine with the aid of an anti-brush border antibody. Cephamandol, cephazolin and cephalothin were completely without effect on the proximal tubule. Cephacetrile, on the other hand, showed clear reactions in 9 out of 15 subjects, in the form of elevated AAP activity in urine and in 6 of the cases membrane elimination was demonstrable immunologically. After withdrawal of the medication, the values of the responder group returned spontaneously to normal, i.e. no cumulative effect was detected. These investigations show that elimination of alanine-aminopeptidase in the urine is a very sensitive index of the action of cephalosporins on renal tubules.


Sodium NMR relaxation in porous materials.
The NMR relaxation of hydrogen nuclei of a fluid in a porous material is generally interpreted in terms of the Brownstein-Tarr model, in which the relaxation rate of the signal is inversely proportional to the pore size. We have investigated whether this model can be applied to the relaxation of Na nuclei in a NaCl solution in a porous material. The results indicate that the ion distribution over the pores can be obtained from an analysis of the Na NMR signal decay, if the pore sizes are roughly below 1 microm. This information is very useful for studies of combined moisture and ion transport in porous building materials.


Discovery of novel, potent and orally efficacious inhibitor of neutral amino acid transporter B0AT1 (SLC6A19).
Amino acid restriction by inhibition of neutral amino acid transporter, B0AT1 (SLC6A19) activity has been recently shown to improve glyceamic control by upregulating glucagon like peptide (GLP1) and fibroblast growth factor (FGF21) in mice. Hence, pharmacological inhibition of B0AT1 is expected to treat type-2 diabetes and related disorder. In this study, rationally designed trifluoromethyl sulfonyl derivatives were identified as novel, potent and orally bioavailable B0AT1 inhibitors. Compound 39 was found to be nanomolar potent (IC50: 0.035 µM) B0AT1 inhibitor with excellent pharmacokinetic profile (%F: 66) in mice and efficacious in vivo in diet induced obese (DIO) mice model.


Starch nanofibers as vehicles for folic acid supplementation: thermal treatment, UVA irradiation and in vitro simulation of digestion.
The supplementation of folic acid in food is essential in the human diet. The present study aimed to encapsulate folic acid at different concentrations (5, 10 and 15% (w/w) on a dry basis) in potato starch nanofibers produced through electrospinning. The starch/folic acid nanofibers were evaluated through morphology, Fourier transform infrared (FTIR) spectra, thermal properties, encapsulation efficiency (EE) and in vitro simulation of the human digestion. The nanofibers were also evaluated based on the folic acid content after thermal treatment (100 and 180 °C) and UVA irradiation (1 and 24 h). Folic acid incorporation influenced the morphology of the nanofibers to display a homogeneous and beadless morphology for nanofibers containing 15% folic acid compared with the other nanofibers (0, 5 and 10% folic acid). The mean diameter varied from 75 to 81 nm. Folic acid characteristic bands and peaks were not found in the nanofiber FTIR spectra and thermograms, respectively. The EE was 73, 87 and 95% for nanofibers with 5, 10 and 15% folic acid, respectively. The starch nanofibers protected folic acid from high temperature and UVA irradiation and during in vitro digestion, showing a release of the vitamin at the end of the simulation (intestinal conditions). The supplementation of folic acid in foods can be effectively achieved by its encapsulation into starch nanofibers, to ensure its protection and controlled release. © 2020 Society of Chemical Industry.


Univariate analysis of factors correlated with tumor control probability of three-dimensional conformal hypofractionated high-dose radiotherapy for small pulmonary or hepatic tumors.
To show the factors correlated with tumor control probability (TCP) after three-dimensional conformal hypofractionated high-dose radiotherapy (3D-CHHRT) for small pulmonary or hepatic tumors. We enrolled 34 patients with 42 lesions (13 lung carcinomas, 6 hepatocellular carcinomas, and 23 lung or liver metastases) treated with 3D-CHHRT alone, with simple immobilization devices, between July 1997 and January 2002. We prescribed 45 Gy in three fractions at the 90-100% isodose line of the planning target volume. The median follow-up period was 18 months (range, 4-46 months). We calculated the TCP using the Kaplan-Meier method and univariate analysis for the following factors: age, gender, primary site, histologic type, tumor size, and previous treatment. Overall, the 2-year TCP of 3D-CHHRT was 83.6%. Local recurrence was observed in 6 lesions within 1 year after treatment. We showed that tumor size was the only significant factor to correlate with the TCP in univariate analysis. The 2-year TCP for tumors <3 cm or > or =3 cm in diameter was 95.0% and 58.3%, respectively (p = 0.0022). No severe adverse effects were observed. The TCP for tumors <3 cm in diameter was excellent for 3D-CHHRT.


Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma.
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.


Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.
Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.


Molecular analysis of extracellular-superoxide dismutase gene associated with high level in serum.
Extracellular-superoxide dismutase (EC-SOD) is one of the SOD isozymes mainly distributed in the extracellular fluid. In the vascular system, it is located on the endothelial cell surface according to studies on the heparin binding capacity. By measurement of serum EC-SOD levels of Japanese in healthy persons (n = 103) and hemodialysis patients (n = 150), 7 healthy subjects and 24 hemodialysis patients were classified into group II associated with high EC-SOD levels. By molecular analysis of the EC-SOD coding region from the group II individuals in Sweden, a single nucleotide substitution of G to C generating an amino acid change of arginine to glycine has been identified in the region associated with the heparin affinity of the enzyme. The same mutation was detected in the Japanese as a homozygote in both alleles of 2 hemodialysis patients and as a heterozygote in one allele of all the healthy group II individuals and 17 hemodialysis patients. The amino acid substitution may result in the decrease of the heparin affinity which is favorable for the existence of EC-SOD in the serum.


A Randomized Clinical Trial of Primary Care Brief Mindfulness Training for Veterans with PTSD.
Primary care (PC) patients typically do not receive adequate posttraumatic stress disorder (PTSD) treatment. This study tested if a brief mindfulness training (BMT) offered in PC can decrease PTSD severity. VA PC patients with PTSD (N = 62) were recruited for a randomized clinical trial comparing PCBMT with PC treatment as usual. PCBMT is a 4-session program adapted from mindfulness-based stress reduction. PTSD severity decreased in both conditions, although PCBMT completers reported significantly larger decreases in PTSD and depression from pre- to posttreatment and maintained gains at the 8-week follow-up compared with the control group. Exploratory analyses revealed that the describing, nonjudging, and acting with awareness facets of mindfulness may account for decreases in PTSD. Our data support preliminary efficacy of BMT for Veterans with PTSD. Whether PCBMT facilitates engagement into, or improves outcomes of, full-length empirically supported treatment for PTSD remains to be evaluated.


Do sex and race/ethnicity influence CD4 cell response in patients who achieve virologic suppression during antiretroviral therapy?
To determine whether CD4 cell count response to virus suppression during highly active antiretroviral therapy differs according to sex or race/ethnicity, we analyzed data in our observational cohort study for patients receiving their first antiretroviral regimen who experienced virus suppression by 6 months of therapy. In both univariate and multivariate analyses, women had greater CD4 cell count increases, compared with men, as did patients receiving a regimen that did not include a protease inhibitor. Race/ethnicity was not a factor.


Discovery and biological evaluation of cholic acid derivatives as potent TGR5 positive allosteric modulators.
In this study, twenty-two novel cholic acid (CA) derivatives were designed and synthesized as potential Takeda G protein-coupled receptor 5 (TGR5) positive allosteric modulators (PAMs) using structure-based drug design (SBDD). GloSensor cAMP accumulation assay was employed to assess the functional activity and allosteric mechanism of final compounds. Biological results showed that all target compounds were able to activate the TGR5 in the cAMP formation assay. Remarkably, compound B1, selective methylation of 7-OH in CA, exhibited 5-fold higher activity for TGR5 compared to that of CA. Moreover, B1 positively modulate the functional activity of chenodeoxycholic acid (CDCA) in TGR5, indicating that B1 is a TGR5 PAM. On the other hand, 12-carbonyl derivative A1 displayed 7-fold higher potency for TGR5 relative to CA. Unexpectedly, compound A1 exhibited the same positive allosteric effect as B1, suggesting that A1 is a TGR5 PAM as well. Molecular modeling study revealed that 12-carbonyl in A1 and 12-OH in B1 formed H-bolds with the key amino acid Thr131, which are significant for TGR5 allosteric property. Taken together, we found two potent TGR5 PAMs A1 and B1 through SBDD, which could be used as lead compounds to further study TGR5 allosteric functionality.


Epitaxial overgrowth of apatite crystals on the thin-ribbon precursor at early stages of porcine enamel mineralization.
The aim of the present work was to investigate changes in cross-sectional morphologies of enamel crystallites as a function of location in secretory porcine enamel. Enamel tissues were obtained from 5- to 6-month-old slaughtered piglets. For examination by electron microscopy, a portion of the secretory enamel was embedded in resin and ultrathin sections were prepared with a diamond knife. In parallel studies, compositional and structural changes of enamel mineral were assessed by chemical analysis and Fourier transform infrared (FTIR) spectroscopy. For this purpose, two consecutive layers of the outer secretory enamel, each approximately 30 microns thick, were separated from the labial side of permanent incisors. Using high-resolution electron microscopy, early events of enamel crystal growth were characterized as the epitaxial growth of small apatite units on the lateral surfaces of the initially precipitated thin ribbon. These apatite units had regular triangle or trapezoid cross-sections. After fusions of those isolated trapezoids on both lateral sides of the platy template, the resulting enamel crystallites had the well-documented flattened-hexagonal shapes in cross-sections. The initially precipitated thin plate was buried inside the overgrown apatite lamella and then retained as a central dark line. Similar morphological evidence for the epitaxial nucleation and overgrowth of carbonatoapatite on the platy template was obtained in vitro. Chemical and FTIR analyses of the enamel layer samples showed that the characteristics of the youngest enamel mineral were distinct from those of enamel crystals found in older secretory enamel.(ABSTRACT TRUNCATED AT 250 WORDS)


The management of portal hypertension.
Portal hypertension is an almost unavoidable complication of cirrhosis, and it is responsible for the more lethal complications of this syndrome. Appearance of these complications represents the major cause of death and liver transplantation in patients who have cirrhosis. This article highlights treatment modalities in use for managing portal hypertension and those that may be available in the future.


Polyfunctional indole-3-carbinol derivatives: 1-(indol-3-yl)glycerols and related compounds, beta-hydroxytryptamines and ascorbigens. Chemistry and biological properties.
Earlier interaction of indole-3-carbinols with L-ascorbic acid and chemical and biological properties of formed 2-skatylderivatives of L-ascorbic acid (ascorbigens) were discussed. In this presentation the properties and stereochemistry of products of interaction of polyfunctional biologically important indole-3-carbinols (indoleglycerol analogs and beta-hydroxytryptamine derivatives) with L-ascorbic acid are investigated. Biological significance of this reaction is discussed.


"TUBEROUS BREAST: A WIDE SPECTRUM OF FEATURES OF THE SAME DISORDER. 13-YEAR EXPERIENCE-BASED CLASSIFICATION AND RECONSTRUCTIVE ALGORITHM".
Due to the multitude of variants in which tuberous breast (TB) deformity could appear, a reconstructive algorithm could help to assess all features that affects the breast and, therefore, planning the most appropriate surgical strategy to correct the malformation. Although in the literature several efficient techniques have been successfully described, the authors propose their experience to standardize a diagnostic and therapeutic approach. The aim of this article is to assess the peculiar pathologic hallmarks of each type of deformity and to propose a one-step reconstructive algorithm tailored on the distinctive patients' characteristics, based on the use of three different adipo-glandular flaps. From September 2006 to December 2019, 118 patients have been treated for TB deformity in one-step procedure using tailored local flaps according to the preoperatively assessed clinical variant. Minimum follow-up was 12 months. All the procedures were performed under local anesthesia. A total of 220 TBs (98 hypoplastic and 122 normoplastic) were treated. Patients' mean age was 20.2 years. Mean follow-up was 36.5 months. 6 minor complications (capsular contracture and nipple-areolar-complex hypoesthesia) and no major complications have been reported. In 9% of cases, minor secondary procedures, including lipofilling, scar revisions and breast implant substitution, have been performed. The proposed algorithm, including a comprehensive classification, preoperative planning and surgical approach derived from authors' experience, aims to propose a tailored surgical approach for each type of tuberous breast deformity.


CircRNA circ_0000554 promotes ovarian cancer invasion and proliferation by regulating miR-567.
Circular RNAs (circRNAs) indicated potential modulating effects in tumor development. However, the specific role of circ_0000554 in ovarian tumor remains unknown. We found that circ_0000554 was overexpressed in ovarian tumor specimens and cells. Forced expression of circ_0000554 promoted cell growth, invasion, and epithelial to mesenchymal transition (EMT). We illustrated that miR-567 was downregulated in ovarian tumor specimens and cells. circ_0000554 was negatively correlated with miR-567 in ovarian tumor specimens. circ_0000554 sponged miR-567 expression in ovarian tumor. RIP assay showed that elevated expression of miR-567 could be enriched with circ_0000554. Luciferase reporter assay indicated that luciferase intensity was inhibited after treated with miR-567 mimic; however, the luciferase value of mut type was not decreased. Elevated expression of circ_0000554 suppressed miR-567 expression in HO8910 cell. circ_0000554 promoted ovarian tumor cell growth, invasion, and EMT via sponging miR-567. It suggested that circ_0000554 represent a potential therapy target for ovarian tumor.


Data on the identity and myristoylation state of recombinant, purified hippocalcin.
In this data article we report on the purity and post translation modification of bacterially expressed and purified recombinant hippocalcin (HPCA): a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. MALDI-TOF in source decay (ISD) analysis was used to identify both the myristoylated or non-myristoylated forms of the protein. MALDI-TOF ISD data on the identity of the protein, amino acid sequence and myristoylation efficiency are provided. This data relates to the article "Single-Column Purification of the Tag-free, Recombinant Form of the Neuronal Calcium Sensor Protein, Hippocalcin Expressed in Eschericia coli" [1].


Inhibition of GSK-3β restores delayed gastric emptying in obesity-induced diabetic female mice.
Diabetic gastroparesis (DG) is a clinical syndrome characterized by delayed gastric emptying (DGE). Loss of nuclear factor erythroid 2-related factor 2 (Nrf2) is associated with reduced neuronal nitric oxide synthase-α (nNOSα)-mediated gastric motility and DGE. Previous studies have shown that nuclear exclusion and inactivation of Nrf2 is partly regulated by glycogen synthase kinase 3β (GSK-3β). In the current study, the molecular signaling of GSK-3β-mediated Nrf2 activation and its mechanistic role on DG were investigated in high-fat diet (HFD)-induced obese/Type 2 diabetes (T2D) female mice. Adult female C57BL/6J mice were fed with HFD or normal diet (ND) with or without GSK-3β inhibitor (SB 216763, 10 mg/kg body wt ip) start from the 14th wk and continued feeding mice for an additional 3-wk time period. Our results show that treatment with GSK-3β inhibitor SB attenuated DGE in obese/T2D mice. Treatment with SB restored impaired gastric 1) Nrf2 and phase II antioxidant enzymes through PI3K/ERK/AKT-mediated pathway, 2) tetrahydrobiopterin (BH4, cofactor of nNOS) biosynthesis enzyme dihydrofolate reductase, and 3) nNOSα dimerization in obese/T2 diabetic female mice. SB treatment normalized caspase 3 activity and downstream GSK-3β signaling in the gastric tissues of the obese/T2 diabetic female mice. In addition, GSK-3β inhibitor restored impaired nitrergic relaxation in hyperglycemic conditions. Finally, SB treatment reduced GSK3 marker, pTau in adult primary enteric neuronal cells. These findings emphasize the importance of GSK-3β on regulating gastric Nrf2 and nitrergic mediated gastric emptying in obese/diabetic rodents.NEW & NOTEWORTHY Inhibition of glycogen synthase kinase 3β (GSK-3β) with SB 216763 attenuates delayed gastric emptying through gastric nuclear factor erythroid 2-related factor 2 (Nrf2)-phase II enzymes in high-fat diet-fed female mice. SB 216763 restored impaired gastric PI3K/AKT/ β-catenin/caspase 3 expression. Inhibition of GSK-3β normalized gastric dihydrofolate reductase, neuronal nitric oxide synthase-α expression, dimerization and nitrergic relaxation. SB 216763 normalized both serum estrogen and nitrate levels in female obese/Type 2 diabetes mice. SB 216763 reduced downstream signaling of GSK-3β in enteric neuronal cells in vitro.


Report on von Willebrand Disease in Malaysia.
Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia. Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013. This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013. Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD. This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013.


Do resin cement viscosity and ceramic surface etching influence the fatigue performance of bonded lithium disilicate glass-ceramic crowns?
To assess the effects of a resin cement in high and low viscosity and distinct conditioning of the intaglio surface of lithium disilicate glass-ceramic crowns on fatigue performance of the crowns. Prosthetic preparations (full-crown) in resin epoxy and crowns in lithium disilicate glass-ceramic were machined and allocated considering 2 factors (n = 10): "surface treatment" (HF - 5% hydrofluoric acid etching, followed by silane application; or E&P-self-etching ceramic primer) and "resin cement" (high or low viscosity). The preparations were etched with 10% hydrofluoric acid and an adhesive was applied. The intaglio surfaces of the ceramic crowns were treated as aforementioned (HF or E&P) and luted with high or low viscosity. The bonded sets were subjected to fatigue testing (step-stress approach: initial load of 200 N, step-size of 50 N, 10,000 cycles/step, 20 Hz) and complementary analyses (fractographic, topographic, and cross-sectional bonded interfacial zone analyses) were performed. Treatment with HF and silane with high viscosity resin cement (955 N/156,000 cycles) and E&P with low viscosity resin cement (1090 N/183,000 cycles) showed the best fatigue performance (statistical similarity between them). The failures originated from defects of the cement-ceramic interface, and the HF treatment induced a more pronounced topographical alteration. Distinct topographical patterns from the HF and E&P treatments induced better fatigue results for the specific viscosity of the resin cement. Therefore, the fatigue performance depended on the existing topography, type of intaglio surface's defects/irregularities after surface treatment, and how the luting agent filled the irregularities.


Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids.
Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 μg/day) and fluticasone propionate (100 μg/day), in infants and preschool children with asthma. The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 μg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.


Tuberculous Abscess of the Chest Wall Simulate Pyogenic Abscess.
The chest wall tuberculosis abscesses is rare. We present a case of a 27-year-old immunocompetent male who presented chest wall abscesses. Imaging (chest radiographic, ultrasound, and computed tomography) and Ziehl-Neelsen staining demonstrated chest wall tuberculosis abscesses.


Fiber-tracking method reveals sensorimotor pathway involvement in stroke patients.
We tested the feasibility of a new MRI technique that provides visualization of the sensorimotor tracts in vivo in a group of stroke victims. Fourteen patients with small infarctions involving the white matter of the supratentorial brain were evaluated. Sensorimotor tracts on the lesional and contralesional sides were successfully depicted in all cases. The position of the sensorimotor tracts relative to the infarct was in good agreement with clinical symptoms. The overall sensitivity and specificity for sensorimotor tract involvement were 100% and 77%, respectively. Our proposed fiber-tracking method was shown to be a clinically feasible technique that correlates well with clinical symptoms.


Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.
To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.


Confined blood chimerism in a monochorionic dizygotic sex discordant twin pregnancy conceived after induced ovulation.
Monochorionic twins are generally considered as a monozygotic twin pregnancy. However, several cases of monochorial dizygotic twin pregnancies have been reported. We report on a rare case of monochorionic dizygotic twin pregnancy conceived after induced ovulation in a 32-year-old woman. The diagnosis was made on morphological ultrasound examination at 18+4 weeks of gestation, showing two fetuses with discordant sex. The amniocentesis was declined by the patient. The monochorionic status was confirmed after a histopathalogical study of the placenta. At delivery, both a phenotypically normal boy and a phenotypically normal girl without sexual abnormality were observed. This analysis also revealed the presence of vascular anastomoses between both fetal circulations. Postnatal cytogenetic analyses indicated the presence of a chimerism in peripheral blood lymphocytes. This chimerism was not observed in cells obtained from a buccal swab. Molecular determination of zygosity confirmed the existence of the confined peripheral blood chimerism with the presence of four parental alleles. We report on a case of monochorionic dizygotic twin pregnancy. This observation underlies the need to carefully assess twin pregnancies, especially when obtained after assisted reproductive technology.


[Cytochemical studies of the alkaline leucocyte phosphatase activity (ALPh-A) in ageing and old patients suffering from acute pneumonia (author's transl)].
1. An ALPh activity increase is evident up to advanced age in patients suffering from unspecific acute pneumonia 2. In ageing and old patients, the ALPh activity diminishes manifestly with increasing age 3. ALPh-A diminishes at a slower rate with increasing age than the left shift according to Schilling 4. Cytochemical examination of the ALPh-A can be successfully used for obtaining reliable clinical and paraclinical diagnoses of acute pneumonia.


Bioremediation potential of a highly mercury resistant bacterial strain Sphingobium SA2 isolated from contaminated soil.
A mercury resistant bacterial strain, SA2, was isolated from soil contaminated with mercury. The 16S rRNA gene sequence of this isolate showed 99% sequence similarity to the genera Sphingobium and Sphingomonas of α-proteobacteria group. However, the isolate formed a distinct phyletic line with the genus Sphingobium suggesting the strain belongs to Sphingobium sp. Toxicity studies indicated resistance to high levels of mercury with estimated EC50 values 4.5 mg L(-1) and 44.15 mg L(-1) and MIC values 5.1 mg L(-1) and 48.48 mg L(-1) in minimal and rich media, respectively. The strain SA2 was able to volatilize mercury by producing mercuric reductase enzyme which makes it potential candidate for remediating mercury. ICP-QQQ-MS analysis of Hg supplemented culture solutions confirmed that almost 79% mercury in the culture suspension was volatilized in 6 h. A very small amount of mercury was observed to accumulate in cell pellets which was also evident according to ESEM-EDX analysis. The mercuric reductase gene merA was amplified and sequenced. The deduced amino acid sequence demonstrated sequence homology with α-proteobacteria and Ascomycota group.


Microbial approaches for sustainable remediation of dye-contaminated wastewater: a review.
The coloured effluents produced from different industries, such as textile, plastics, printing, cosmetics, leather and paper, are extremely toxic and a tremendous threat to the aquatic organisms and human beings. The removal of coloured dye pollutants from the aqueous environment is a great challenge and a pressing task. The growing demand for low-cost and efficient treatment approaches has given rise to alternative and eco-friendly methods, such as biodegradation and microbial remediation. This work summarizes the overview and current research on the remediation of dye pollutants from the aqueous environment by microbial bio-sorbents, such as bacteria, fungi, algae, and yeast. In addition, dye degradation capabilities of microbial enzymes have been highlighted and discussed. Further, the influence of various experimental parameters, such as temperature, pH, and concentrations of nutrients, and dye, has been summarized. The proposed mechanism for dye removal by microorganisms is also discussed. The object of this review is to provide a state-of-the-art of microbial remediation technologies in eliminating dye pollutants from water resources.


Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor.
In the wild-type tachykinin NK3A receptor histidyl residues are present at two positions in TM-V, V:01 and V:05, at which Zn2+ functions as an antagonist in NK1 and kappa-opioid receptors with engineered metal-ion sites. Surprisingly, in the NK3A receptor Zn2+ instead increased the binding of the agonist 125I-[MePhe7]neurokinin B to 150%. [MePhe7]neurokinin B bound to the NK3A receptor in a two-component mode of which Zn2+ eliminated the subnanomolar binding mode but induced a higher binding capacity of the nanomolar binding mode. Signal transduction was not induced by ZnCl2 but 10 microM ZnCl2 enhanced the effect of neurokinin B. Ala-substitution of HisV:01 eliminated the enhancing effect of Zn2+ on peptide binding. It is concluded that physiological concentrations of Zn2+ have a positive modulatory effect on the binding and function of neurokinin B on the NK3A receptor through a bis-His site in TM-V.


Association of plasma C-reactive protein levels with the diagnosis of Alzheimer's disease.
C-reactive protein (CRP) participates in the systemic response to inflammation. Previous studies report inconsistent findings regarding the relationship between plasma CRP and Alzheimer's disease (AD). We measured plasma CRP in 203 subjects with AD, 58 subjects with mild cognitive impairment (MCI) and 117 normal aging subjects and administered annual Mini-Mental State Examinations (MMSE) during a 3-year follow-up period to investigate CRP's relationship with diagnosis and progression of cognitive decline. Adjusted for age, sex, and education, subjects with AD had significantly lower levels of plasma CRP than subjects with MCI and normal aging. However, there was no significant association between plasma CRP at baseline and subsequent cognitive decline as assessed by longitudinal changes in MMSE score. Our results support previous reports of reduced levels of plasma CRP in AD and indicate its potential utility as a biomarker for the diagnosis of AD.


A simple electrochemical immunosensor based on a gold nanoparticle monolayer electrode for neutrophil gelatinase-associated lipocalin detection.
An electrochemical immunosensor for the accurate detection of cat neutrophil gelatinase-associated lipocalin (NGAL) in urine samples based on an electrode with a monolayer of gold nanoparticles (AuNPs) was proposed in this study. To fabricate the sensing electrode, a nickel mold with concave micron hemisphere array was prepared and then used to transfer the micron hemispherical structure onto a polyethylene terephthalate (PET) film using the hot embossing technique. A gold thin film was sputtered onto the micron hemispherical structure array, after which 1,6-hexanedithol and AuNPs were uniformly deposited on the PET membrane to form a sensing electrode. The NGAL concentrations were measured by electrochemical impedance spectroscopy after attaching the anti-NGAL. Results revealed that the proposed sensing scheme exhibited a wide dynamic detection range from 1 to 100 ng/mL, which is far enough to distinguish the healthy (NGAL concentration <10 ng/mL) from the damaged kidney. A low limit of detection and high sensitivity of 0.47 ng/mL and 10261.8 Ω ng-1mL, respectively, were also measured. After performing real sample detection using urine samples from cats collected at a veterinary hospital, the results confirmed that the proposed NGAL detection approach in this research could accurately detect the concentration of NGAL in cat urine samples.


Free breathing three-dimensional cardiac quantitative susceptibility mapping for differential cardiac chamber blood oxygenation - initial validation in patients with cardiovascular disease inclusive of direct comparison to invasive catheterization.
Differential blood oxygenation between left (LV) and right ventricles (RV; ΔSaO2) is a key index of cardiac performance; LV dysfunction yields increased RV blood pool deoxygenation. Deoxyhemoglobin increases blood magnetic susceptibility, which can be measured using an emerging cardiovascular magnetic resonance (CMR) technique, Quantitative Susceptibility Mapping (QSM) - a concept previously demonstrated in healthy subjects using a breath-hold 2D imaging approach (2DBHQSM). This study tested utility of a novel 3D free-breathing QSM approach (3DNAVQSM) in normative controls, and validated 3DNAVQSM for non-invasive ΔSaO2 quantification in patients undergoing invasive cardiac catheterization (cath). Initial control (n = 10) testing compared 2DBHQSM (ECG-triggered 2D gradient echo acquired at end-expiration) and 3DNAVQSM (ECG-triggered navigator gated gradient echo acquired in free breathing using a phase-ordered automatic window selection algorithm to partition data based on diaphragm position). Clinical testing was subsequently performed in patients being considered for cath, including 3DNAVQSM comparison to cine-CMR quantified LV function (n = 39), and invasive-cath quantified ΔSaO2 (n = 15). QSM was acquired using 3 T scanners; analysis was blinded to comparator tests (cine-CMR, cath). 3DNAVQSM generated interpretable QSM in all controls; 2DBHQSM was successful in 6/10. Among controls in whom both pulse sequences were successful, RV/LV susceptibility difference (and ΔSaO2) were not significantly different between 3DNAVQSM and 2DBHQSM (252 ± 39 ppb [17.5 ± 3.1%] vs. 211 ± 29 ppb [14.7 ± 2.0%]; p = 0.39). Acquisition times were 30% lower with 3DNAVQSM (4.7 ± 0.9 vs. 6.7 ± 0.5 min, p = 0.002), paralleling a trend towards lower LV mis-registration on 3DNAVQSM (p = 0.14). Among cardiac patients (63 ± 10y, 56% CAD) 3DNAVQSM was successful in 87% (34/39) and yielded higher ΔSaO2 (24.9 ± 6.1%) than in controls (p < 0.001). QSM-calculated ΔSaO2 was higher among patients with LV dysfunction as measured on cine-CMR based on left ventricular ejection fraction (29.4 ± 5.9% vs. 20.9 ± 5.7%, p < 0.001) or stroke volume (27.9 ± 7.5% vs. 22.4 ± 5.5%, p = 0.013). Cath measurements (n = 15) obtained within a mean interval of 4 ± 3 days from CMR demonstrated 3DNAVQSM to yield high correlation (r = 0.87, p < 0.001), small bias (- 0.1%), and good limits of agreement (±8.6%) with invasively measured ΔSaO2. 3DNAVQSM provides a novel means of assessing cardiac performance. Differential susceptibility between the LV and RV is increased in patients with cine-CMR evidence of LV systolic dysfunction; QSM-quantified ΔSaO2 yields high correlation and good agreement with the reference of invasively-quantified ΔSaO2.


Susceptibility of mycobacteria to fusidic acid.
Fusidic acid was shown to be effective in vitro against 30 clinical isolates of Mycobacterium tuberculosis at concentrations of 32-64 mg/l, concentrations which are readily achieved in serum. All but one of 17 Mycobacterium avium complex strains were resistant to fusidic acid at concentrations up to 64 mg/l. However, synergistic effects were shown for 11 of the 17 strains when fusidic acid was combined with ethambutol. Five of the strains were fully susceptible to the combination of fusidic acid (64 mg/l) and ethambutol (4 mg/l). It is suggested that fusidic acid should be evaluated clinically as a potential supplementary drug for treatment of mycobacterial infections.