The Cephenniini of China. VII. New species and new records of Cephennodes Reitter of Shaanxi, Gansu and Sichuan (Coleoptera: Staphylinidae: Scydmaeninae).
Nine new Chinese species of Cephennodes are described: C. (s. str.) intricatus sp. n. (Gansu), C. (s. str.) cryptointricatus sp. n. (Gansu), C. (s. str.) monofoveatus sp. n. (Shaanxi), C. (s. str.) pinnapes sp. n. (Sichuan), C. (s. str.) elegantissimus sp. n. (Sichuan), C. (s. str.) palpalis sp. n. (Gansu), C. (Fusionodes) corpulentus sp. n. (Sichuan), C. (Fusionodes) gutta sp. n. (Shaanxi) and C. (Fusionodes) medusa sp. n. (Sichuan). Cephennodes elegantissimus and C. palpalis are not placed in any species group within Cephennodes, while the remaining new taxa belong to the excavatus group (C. intricatus and C. cryptointricatus), the taurus group (C. monofoveatus), the inflatipes group (C. pinnapes), the graeseri group (C. gutta and C. medusa) and the newly established serratus group (C. corpulentus). Additionally, new records of previously described species are given: C. (s. str.) subcaudatus Jałoszyński (Shaanxi), C. (s. str.) parabdominalis Jałoszyński (Shaanxi) and C. (s. str.) pteroscapus Jałoszyński (Sichuan).


Half-rotation in a [2]catenane via interconvertible Pd(II) coordination modes.
Reaction of a [2]catenane with Pd(OAc)2 binds both macrocycles to the metal, locking them in position; treatment with PdCl2, however, results in coordination of only one ring, producing a half-turn in the relative orientation of the [2]catenane components in both solution and the solid state.


Manufacture of antibacterial carbon fiber-reinforced plastics (CFRP) using imine-based epoxy vitrimer for medical application.
An antibacterial carbon fiber-reinforced plastics (CFRP) was manufactured based on a vitrimer containing imine groups. A liquid curing agent was prepared to include an imine group in the matrix, and was synthesized without a simple mixing reaction and any purification process. The vitrimer used as the matrix for CFRP was prepared by reacting a commercial epoxy with a synthesized curing agent. The structural and thermal properties of the vitrimer were determined by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In addition, the temperature-dependent behavior of the vitrimer was characterized by stress relaxation, reshaping, and shape memory experiments. The mechanical properties of composites fabricated using vitrimer were fully analyzed by tensile, flexural, short-beam strength, and Izod impact tests and had mechanical properties similar to reference material. Moreover, both the vitrimer and the vitrimer composites showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coil due to the imine group inside the vitrimer. Therefore, vitrimer composites have potential for applications requiring antimicrobial properties, such as medical devices.


Normal right ventricular systolic and diastolic function assessed by krypton-81m equilibrium ventriculography.
Krypton-81m equilibrium ventriculography was used to study right ventricular function in 23 healthy male volunteers. Technetium-99m lung perfusion scintigraphy was employed to subtract radionuclide activity within lung during image analysis thereby enhancing image quality. The imaging technique was used to generate a time-activity curve for the right ventricle allowing the definition of indices of normal systolic and diastolic function for the right ventricle. At rest, indices of systolic ejection and diastolic filling were comparable to those previously reported for the left ventricle. Using the imaging technique, movement artifact during exercise reduces image quality and limits accurate measurement of these indices to resting studies.


Serum IgE Levels: An Effective Diagnostic Tool for Evaluation and Monitoring of Orbital Fungal Granuloma.
To determine the changes in IgE levels in diagnosis and postoperative monitoring of orbital fungal granuloma. Descriptive analytical study. Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from July 2012 to June 2013. Cases with clinically high index of suspicion for orbital fungal granuloma and 50 healthy volunteers were inducted as control subjects. Patients with recurrent cases of orbital fungal granuloma, previous orbital surgery, and those with very low clinical suspicion of fungal granuloma were excluded. Total serum IgE level (IU/ml), eosinophil counts and skin prick test were performed in all subjects. Independent t-test was used for comparison of healthy volunteers and patients with biopsy proven orbital fungal granuloma. Repeated measures ANOVA was used for comparing the preoperative and postoperative total serum IgE level of patients with biopsy proven fungal granuloma. The mean total serum IgE level for the healthy volunteers was 208.82 ±41.43 IU/ml. The mean pre-operative IgE value of histologically confirmed cases of fungal granuloma was 1613.72 ±282.83 IU/ml. The total serum IgE level gradually declined after surgery and anti-fungal treatment. The mean serum IgE level 3, 6 and 9 months postoperatively were 1039.48 ±308.40, 568.77 ±162.01 and 224.92 ±51.55 IU/ml respectively. These tests showed that the drop in IgE level in cases of fungal granuloma with treatment was statistically significant (p < 0.001). Total serum IgE level can be used as a reliable diagnostic and postoperative monitoring tool in orbital fungal granuloma.


Glutathione protects PC12 cells from ascorbate- and dopamine-induced apoptosis.
The role of reduced glutathione (GSH) on ascorbate- and dopamine-induced apoptosis in PC12 cells was investigated. Ascorbate is a potent reducing agent and is thus expected to protect against dopamine-induced apoptosis. However, we found that both ascorbate and dopamine killed PC12 cells and ascorbate enhanced dopamine-induced toxicity. The EC50 of cell toxicity induced by ascorbate, dopamine and dopamine plus 0.1 mM ascorbate during 24-h treatment were 0.93+/-0.15 mM, 0.18+/-0.05 mM and 0.13+/-0.04 mM, respectively. When the medium contained 10 mM GSH, the EC50 increased approximately three- and sevenfold for ascorbate and dopamine, respectively. With increased treatment duration, no further toxic effects of ascorbate or dopamine were observed. The GSH synthesis inhibitor, DL-buthionine-(S,R)-sulfoximine (BSO), induced cell toxicity and potentiated the toxic effects of ascorbate and dopamine, suggesting that endogenous GSH participates in protecting against basal oxidative stress. We conclude that both ascorbate and dopamine induce apoptosis in PC12 cells and further that GSH protects them from apoptosis. This study indicates that the toxic effects of ascorbate are potentially due to an oxidative mechanism, similar to that induced by dopamine.


The Golden Letter: Innovation Collaboration to Reduce Avoidable Hospital Admissions.
Emergency Department (ED) overutilization and avoidable hospital admissions have been identified as areas of improvement. Studies have shown that ensuring adequate primary care follow-up after discharge from ED is an area that can be targeted to help decrease hospitalizations. Between April 2017 and December 2018, any family medicine patient presented by the ED for admission who was determined to be a candidate for rapid primary care follow-up, was offered a "Golden Letter." This letter guaranteed that the patient would be evaluated within 48 hours of discharge at the patient's primary care clinic. We studied the impact on reducing hospital admissions, 30-day ED revisits, and 30-day hospitalizations. Our data analysis included gender, age, and insurance status. A total of 191 ED encounters that may have been admitted to the hospital were instead given a golden letter after shared decision making. A total of 104 (54.5%) completed a follow-up appointment within 48 hours. The 30-day ED revisit rate was 34% (65 encounters) with 33 (31.7%) of these patients having completed a follow-up visit and 32 (36.8%) did not follow up. There were 35 (18.3%) hospital admissions within 30 days of the ED visit. Of the patients admitted, 12 (11.5%) completed a follow-up visit and 23 (26.4%) did not complete a follow-up visit. This initiative effectively reduced the number of low-acuity admissions and 30-day hospitalizations. This concept can provide a significant reduction of health care resource utilization and cost by ensuring safe ED discharge and rapid outpatient follow-up for low-acuity patients.


Prevalence of self-reported jaw pain in Germany: two cross-sectional surveys of the general German population.
This study evaluated the prevalence of jaw pain as a local, regional, or widespread pain condition and its association with psychosocial variables in a large representative group of the general population from all regions in Germany. In two representative samples consisting of 2524 and 2515 subjects, respectively, the 7-day and 3-month pain prevalences were measured by using the Regional Pain Scale (RPS). Somatic symptom burden (somatization) and pain-related depression were assessed with the Patient Health Questionnaire and the Somatic Symptom Scale, respectively. Binary logistic regression was chosen to calculate the associations between demographic and psychological clinical predictor variables with jaw pain. The 7-day jaw pain prevalence was 4.0 % (95 % CI = 3.2-4.8). Of the subjects with jaw pain, only 9 % had local pain (1 pain site), while the remaining 91 % reported regional pain (2-5 pain sites), or widespread pain (6-19 pain sites). The 3-month prevalence of generally present jaw pain was 0.9 % (95 % CI = 0.6-1.0). Regional or widespread pain was present in 82 % of the participants. Jaw pain was predicted by somatic symptom burden (past 7 days, OR = 1.15 [95 % CI = 1.09-1.22]; past 3 months, OR = 1.13 [95 % CI = 1.02-1.25]), but not by depression. Most individuals with jaw pain have additional pain in other anatomical regions. They might also exhibit a greater risk for pain-associated somatic symptom burden. Assessment of pain distribution in the whole body and the use of a psychometric screening questionnaire for somatic symptom burden are recommended for individuals presenting with jaw pain in a clinical setting.


Acute Slow Wave Responses to High-Frequency Gastric Electrical Stimulation in Patients With Gastroparesis Defined by High-Resolution Mapping.
High-frequency gastric electrical stimulation (GES) has emerged as a therapy for gastroparesis, but the mechanism(s) of action remain unclear. There is a need to refine stimulation protocols for clinical benefit, but a lack of accurate techniques for assessing mechanisms in clinical trials, such as slow wave modulation, has hindered progress. We thereby aimed to assess acute slow wave responses to GES in gastroparesis patients using high-resolution (HR) (multi-electrode) mapping, across a range of stimulation doses achievable by the Enterra stimulation device (Medtronic Inc., MN, USA). Patients with medically refractory gastroparesis (n = 8) undergoing device implantation underwent intraoperative HR mapping (256 electrodes). Baseline recordings were followed by four protocols of increasing stimulation intensity, with washout periods. Slow wave patterns, frequency, velocity, amplitude, and dysrhythmia rates were quantified by investigators blinded to stimulation settings. There was no difference in slow wave pattern, frequency, velocity, or amplitude between baseline, washout, and stimulation periods (all p > 0.5). Dysrhythmias included ectopic pacemakers, conduction blocks, retrograde propagation, and colliding wavefronts, and dysrhythmia rates were unchanged with stimulation off vs. on (31% vs. 36% duration dysrhythmic; p > 0.5). Symptom scores and gastric emptying were improved at 5.8 month follow-up (p < 0.05). High-frequency GES protocols achievable from a current commercial device did not acutely modulate slow wave activity or dysrhythmias. This study advances clinical methods for identifying and assessing therapeutic GES parameters, and can be applied in future studies on higher-energy protocols and devices.


Dramatic reversal of derangements in muscle metabolism and left ventricular function after bariatric surgery.
The study objective was to define muscle metabolic and cardiovascular changes after surgical intervention in clinically severe obese patients. Obesity is a state of metabolic dysregulation that can lead to maladaptive changes in heart and skeletal muscle, including insulin resistance and heart failure. In a prospective longitudinal study, 43 consecutive patients underwent metabolic profiling, skeletal muscle biopsies, and resting echocardiograms at baseline and 3 and 9 months after bariatric surgery. Body mass index decreased (mean changes, 95% confidence interval [CI]): 7.7 kg/m(2) (95% CI, 6.70-8.89) at 3 months and 5.6 kg/m(2) (95% CI, 4.45-6.80; P<.0001) at 9 months after surgery, with restoration of insulin sensitivity and decreases in plasma leptin at the same time points. Concurrent with these changes were dramatic decreases in skeletal muscle transcript levels of stearoyl coenzyme-A desaturase and pyruvate dehydrogenase kinase-4 at 3 and 9 months (P<.0001, for both) and a significant decrease in peroxisome proliferation activated receptor-alpha-regulated genes at 9 months. Left ventricular relaxation impairment, assessed by tissue Doppler imaging, normalized 9 months after surgery. Weight loss results in the reversal of systemic and muscle metabolic derangements and is accompanied by a normalization of left ventricular diastolic function.


[Restatement and conception of an experimental battery of measurements of displacements in the three planes of a vertebral unit].
The study of motions of a vertebral unit is difficult because of the great number of participating structures. Analysis in the three planes is required to obtain optimal visualization of the entire spectrum of criteria involved. Initially, we used comparators to achieve these measurements. However, the complexity and number of parameters quickly led us to switch to electronic sensors. At present, a completely automated test bench has been developed using an Orion data processing chain. Decoding and interpretating results nevertheless remains difficult in such tridimensional analyses.


Comparative phylogenetic methods and the cultural evolution of medicinal plant use.
Human life depends on plant biodiversity and the ways in which plants are used are culturally determined. Whilst anthropologists have used phylogenetic comparative methods (PCMs) to gain an increasingly sophisticated understanding of the evolution of political, religious, social and material culture, plant use has been almost entirely neglected. Medicinal plants are of special interest because of their role in maintaining people's health across the world. PCMs in particular, and cultural evolutionary theory in general, provide a framework in which to study the diversity of medicinal plant applications cross-culturally, and to infer changes in plant use over time. These methods can be applied to single medicinal plants as well as the entire set of plants used by a culture for medicine, and they account for the non-independence of data when testing for floristic, cultural or other drivers of plant use. With cultural, biological and linguistic diversity under threat, gaining a deeper and broader understanding of the variation of medicinal plant use through time and space is pressing.


Efficacy and safety of laparoscopic common bile duct exploration via choledochotomy with primary closure for the management of acute cholangitis caused by common bile duct stones.
T-tube drainage after laparoscopic common bile duct exploration (LCBDE) has been demonstrated to be safe and effective for patients with acute cholangitis caused by common bile duct stones (CBDSs). The outcomes after LCBDE with primary closure in patients with CBDS-related acute cholangitis are unknown. The present study aimed to evaluate the efficacy and safety of LCBDE with primary closure for the management of acute cholangitis caused by CBDSs. Between June 2015 and June 2020, 368 consecutive patients with choledocholithiasis combined with cholecystolithiasis, who underwent laparoscopic cholecystectomy (LC) + LCBDE in our department, were retrospectively reviewed. A total of 193 patients with CBDS-related acute cholangitis underwent LC + LCBDE with primary closure of the CBD (PC group) and 62 patients underwent LC + LCBDE followed by T-tube placement (T-tube group). A total of 113 patients who did not have cholangitis were excluded. The clinical data were compared and analyzed. There was no mortality in either group. No significant differences were noted in morbidity, bile leakage rate, retained CBD stones, or readmission rate within 30 days between the two groups. Compared with the T-tube group, the PC group avoided T-tube-related complications and had a shorter operative time (121.12 min vs. 143.37 min) and length of postoperative hospital stay (6.59 days vs. 8.81 days). Moreover, the hospital expenses in the PC group were significantly lower than those in the T-tube group ($4844.47 vs. $5717.22). No biliary stricture occurred during a median follow-up of 18 months in any patient. No significant difference between the two groups was observed in the rate of stone recurrence. LCBDE with primary closure is a safe and effective treatment for cholangitis caused by CBDSs. LCBDE with primary closure is not inferior to T-tube drainage for the management of CBDS-related acute cholangitis in suitable patients.


Pediatric Extranodal Lymphoma.
Lymphoma is the third most common pediatric neoplasm. Non-Hodgkin lymphoma (NHL) accounts for nearly half of cases and commonly involves extranodal sites. Compared with adults, this histologic spectrum of pediatric NHL is very narrow and consists of aggressive tumors. Patients typically present with widespread disease. Generally, NHL occurring in children includes Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma. Staging and assessment of therapeutic response are usually based on FDG-PET/CT. Due to the increased susceptibility of young patients to the effects of ionizing radiation, alternative methods of imaging are being explored.


Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort.
Asthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children. We studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex. Among the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23). Our findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.


Notch signaling: mediator and therapeutic target of bone metastasis.
The Notch signaling pathway regulates several distinct cellular programs that are indispensible for proper embryonic development and maintenance of adult tissue homeostasis. Among the various organs of the human body, the pathway has an important role in the bone microenvironment, managing cell-fate decisions in two bone-specific cells. Significantly, pathological activation of the Notch pathway in these cells by metastatic tumor cells promotes osteolytic colonization of the bone. Armed with this knowledge, disruption of the Notch pathway, and other bone microenvironment signaling components that facilitate Notch-mediated bone metastasis, may serve as a viable therapeutic intervention in this aggressive, incurable disease.


[Disturbances of the development of enamel-forming organ as an etiological factor in pulp diseases].
On the basis of a literature survey the author discusses the so called everted odontoma, a developmental anomaly of dental tissues which may lead to diseases of the pulp and periapical tissues. The method is described of treatment of periapical inflammatory conditions which may be due to these anomalies.


Postoperative radiotherapy in the treatment of Ewing tumors: influence of the interval between surgery and radiotherapy.
The impact of the timing of postoperative irradiation was evaluated in patients with Ewing tumors who received postoperative irradiation. 153 patients treated in the CESS 86 and EICESS 92 trials were evaluated in a retrospective analysis. They received surgery and postoperative irradiation as local treatment modalities. In 46 patients, postoperative irradiation was started within 60 days after surgery, in 107 patients after more than 60 days. A median dose of 45 Gy was administered. The median follow-up was 70 months. There was no substantial difference between the two groups concerning risk factors for local failure and survival. The local control rate after 5 years was 98% in the group with early onset of radiation and 92% in the group with later onset (n.s.). There is no difference in event free survival between the two groups (both 64% after 5 years). If the cutpoint of the onset of postoperative irradiation was chosen after 90 days, there was no difference in local control or event free survival. Patients with early onset of postoperative irradiation show a trend for improved local control compared to patients with a later onset; the difference is statistically not significant. This trend has no influence on survival.


Extranodal NK/T-cell lymphoma: Updates in biology and management strategies.
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that is very common in East Asia and Latin America. Two-thirds of patients have localized disease in the nasal cavity or adjacent sites. Large retrospective studies have revealed the clinicopathologic features of ENKL patients, identified risk factors for short survival time, and developed prognostic models. Next-generation sequencing studies have provided a comprehensive list of recurrent mutations in ENKL. Since the early 2000s, disease-specific therapeutic approaches have been developed, and the standard of care for ENKL has markedly changed. Non-anthracycline-containing chemotherapy with or without radiotherapy is the current standard approach for ENKL treatment. Emerging therapies, including the use of immune checkpoint inhibitors, are being investigated.


Bardet-Biedl syndrome 1 genotype and obesity in the Newfoundland population.
Obesity is one of the primary clinical features of Bardet-Biedl Syndrome (BBS), a genetically heterogeneous disorder that is usually inherited as an autosomal recessive trait. It has been suggested that heterozygous carriers of BBS are predisposed to obesity. We set out to identify the common mutation in BBS1 families from southwest Newfoundland and to examine the relationship between this mutation and obesity in the general population. We genotyped BBS1 families from Newfoundland to determine the nature of the mutation causing BBS in this population. We then screened 200 obese individuals (average body mass index (BMI)=37.9 kg/m2; average waist to hip ratio=0.935; average waist=113.8 cm) and 200 ethnically matched, unrelated, controls (average BMI=25.0 kg/m2; average waist to hip ratio=0.896; average waist=86.9 cm) from the same geographic region for the presence of this mutation. All affected members of the six Newfoundland BBS1 families were homozygous for the most common BBS1 mutation (M390R). This mutation was found in the heterozygous state in three of the 200 obese individuals and also in three of the 200 matched controls. The high frequency of BBS1 in Newfoundland appears to be the result of a founder event. Our data do not support the hypothesis that the M390R BBS1 mutation plays a significant role in the frequency of obesity in the general public in Newfoundland.


Metabotropic glutamate 7 (mGlu7) receptor: a target for medication development for the treatment of cocaine dependence.
Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans. Therefore, glutamate receptors, in particular metabotropic glutamate (mGlu) receptors, have become important targets for medication development for the treatment of drug dependence. In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence. Systemic or local administration of AMN082 into the nucleus accumbens (NAc), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self-administration procedure. In addition, AMN082 inhibited the reward-enhancing effects induced by cocaine, as assessed in the intracranial self-stimulation procedure, and cocaine- or cue-induced reinstatement of drug-seeking behavior. In vivo microdialysis studies indicated that systemic or intra-NAc administration of AMN082 significantly decreased extracellular γ-aminobutyric acid (GABA) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non-dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine. Further, data indicated that AMN082-induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission. These increases in extracellular glutamate functionally antagonized cocaine-induced inhibition of NAc-ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine. In addition, elevated extracellular glutamate activated presynaptic mGlu2/3 autoreceptors which in turn inhibited cocaine priming- or cue-induced enhancement of glutamate release and reinstatement of drug-seeking behavior. Taken together, these findings suggest that the mGlu7 receptor is an important target for medication development for the treatment of drug dependence. AMN082 or other mGlu7 receptor allosteric agonists may have potential as novel pharmacotherapies for cocaine addiction. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.


Bradykinin preconditioning improves the profile of cell survival proteins and limits apoptosis after cardioplegic arrest.
We hypothesized that preconditioning the heart with bradykinin (BK) would improve the profile of antiapoptotic proteins and inhibit myocardial apoptosis. Eighteen rabbit hearts were retrogradely perfused with Krebs-Henseleit buffer (KHB). Six control hearts were perfused with KHB for 90 minutes without cardioplegia ischemia. Six hearts were arrested for 30 minutes (37 degrees C) with crystalloid cardioplegia (CCP). Six BK preconditioning (BKPC) hearts received a 10-minute coronary infusion of 10(-8) M BK-enriched KHB followed by a 5-minute recovery period and were then arrested for 30 minutes with CCP. The hearts were reperfused for 30 minutes with KHB. BKPC significantly improved the recovery of left ventricular pressure (73+/-5 versus 51+/-4 mm Hg; P<0.05) and reduced the percentage of myocardial apoptosis (3.4+/-0.3% versus 1.2+/-0.2%; P<0.05) as compared with CCP. There were no significant differences in total protein levels of caspase 3, Bcl-2, Bad, and Bax, among the groups. Both BKPC and CCP induced phosphorylation of Bad at Ser112, but the BKPC group had higher phosphorylated Bad than CCP (4.4+/-0.5 versus 2.0+/-0.3; P<0.05). Both BKPC and CCP alone increased caspase 3 cleavage and activity as compared with controls (P<0.05 and P<0.01, respectively), but BKPC caused less cleavage and activation of caspase 3 than CCP alone (P<0.05). BKPC increased Bad phosphorylation, inhibited caspase 3 activation, and limited myocardial apoptosis, which were associated with improvement of left-ventricular performance. These results identify novel molecular mechanisms underlying the protective effects of BKPC during cardiac surgery.


[The combination of etomidate and fentanyl as a short acting and introduction anaesthesia in the dog in experimental medicine (author's transl)].
The effects of a combination of etomidate (1.0 mg/kg bw) and fetanyl (0.005 mg/kh bw) on haematology, blood gases, acid-base balance and haemodynamics were investigated in 8 mongrel dogs. The only significant change in haematology was leucopenia. Blood gas values and acid-base balance initially showed a depression of respiration and a tendency to slight metabolic acid dosis. Decreased heart rate caused diminution of cardiac output, while systemic and pulmonary resistance as well as stroke volume were not altered significantly.


Influence of gravity on cat vertical vestibulo-ocular reflex.
The vertical vestibulo-ocular reflex (VOR) was recorded in cats using electro-oculography during sinusoidal angular pitch. Peak stimulus velocity was 50%/s over a frequency range from 0.01 to 4.0 Hz. To test the effect of gravity on the vertical VOR, the animal was pitched while sitting upright or lying on its side. Upright pitch changed the cat's orientation relative to gravity, while on-side pitch did not. The cumulative slow component position of the eye during on-side pitch was less symmetric than during upright pitch. Over the mid-frequency range (0.1 to 1.0 Hz), the average gain of the vertical VOR was 14.5% higher during upright pitch than during on-side pitch. At low frequencies (less than 0.05 Hz) changing head position relative to gravity raised the vertical VOR gain and kept the reflex in phase with stimulus velocity. These results indicate that gravity-sensitive mechanisms make the vertical VOR more compensatory.


Adjuvant irradiation for axillary metastases from malignant melanoma.
To evaluate the outcome and treatment-related toxicity for patients with axillary lymph node metastases from malignant melanoma treated with surgery and radiation, with or without systemic therapy. The medical records of 89 consecutive patients with axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients underwent axillary dissection and postoperative radiation to a median dose of 30 Gy at 6 Gy/fraction delivered twice weekly. In 3 patients referred with microscopic residual disease, a single boost (4-6 Gy) was given to a reduced field. All but 2 patients were referred because their axillary dissections revealed features believed to predict a 30-50% risk of subsequent axillary recurrence: lymph nodes >/=3 cm in size (54 patients), >/=4 lymph nodes positive (44), the presence of extracapsular extension (69), recurrent disease after initial surgical resection (23), or multiple risk factors (77). Fifty-one patients received systemic therapy before or after radiation therapy. At a median follow-up of 63 months, 47 patients had relapsed and 43 patients had died. The actuarial overall and disease-free survival rates at 5 years were 50% and 46%, respectively. The actuarial axillary control and distant metastasis-free survival rates at 5 years were 87% and 49%, respectively. Univariate analysis revealed that the probability of axillary control was inferior when the axillary disease measured >6 cm in size (72% vs. 93%, p = 0.02), the location of the primary tumor was unknown (74% vs. 93%, p = 0.02), the axillary failure occurred within 18 months from diagnosis of the primary melanoma (84% vs. 100%, p = 0.04), or the Breslow thickness was >4 mm (80% vs. 96%, p = 0.04). Additionally, there was an inferior distant metastasis-free and disease-free survival when there were >2 nodes positive for metastatic disease, the primary lesion had a Breslow thickness >4 mm, or the axillary failure occurred within 18 months from diagnosis of the primary melanoma. On multivariate analysis, the significantly inferior distant metastasis-free and disease-free survival seen when >2 nodes were positive or the recurrence occurred within 18 months remained significant. The small number of axillary failures precluded multivariate analysis for axillary control; however, stratified analysis suggested that size >6 cm was the factor most closely associated with subsequent axillary failure. Twenty-six patients developed treatment-related arm edema. Classification according to the severity of edema yielded 5-year actuarial arm edema rates of 21%, 19%, and 1%, for Grade 1 (transient or asymptomatic), Grade 2 (requiring medical intervention), or Grade 3 (requiring surgical intervention) edema, respectively. Adjuvant radiation therapy using a hypofractionated regimen resulted in an 87% 5-year axillary control rate, superior to the 50-70% local control achieved with surgery alone for lymph node metastases from melanoma when high-risk features are present. Improvements are needed for patients with bulky nodal masses >6 cm in size. Mild-to-moderate arm edema was common, but manageable. The degree to which radiotherapy adds to the risk of arm edema after axillary dissection alone cannot be addressed in the present analysis.


High-performance liquid chromatographic method for the radiometric determination of [14C] bucromarone in human plasma utilizing non-radiolabeled bucromarone as an internal standard.
A novel radiometric high-performance liquid chromatographic (HPLC) method was developed for the determination of [14C]bucromarone in human plasma. The procedure involved the addition of non-radiolabeled bucromarone hydrochloride to each plasma sample as an internal standard; the plasma sample was then extracted, and the bucromarone was separated from its metabolites and endogenous compounds by reversed phase HPLC. The concentration of [14C]bucromarone in each plasma sample was calculated from the ratio of the amount of radioactivity in the eluate fraction corresponding to bucromarone and the peak height of the ultraviolet absorbance (210 nm) of the non-radiolabeled bucromarone used as an internal standard. The lower limit of quantitation for bucromarone free base in this assay was 8 ng/ml when [14C]bucromarone succinate had a specific activity of 0.5 microCi/mg. The coefficients of variation for the experimentally determined concentrations of bucromarone in spiked plasma samples were 6.8 and 14.3% at concentrations of 80 and 20 ng/ml, respectively. This method was used to determine concentrations of bucromarone in the plasma of healthy volunteers who were given intravenous infusions of [14C]bucromarone succinate. In general, the methodology should be applicable to any radiolabeled compound that possesses appreciable ultraviolet absorbance.


Influence of physical properties of solid biomass fuels on the design and cost of storage installations.
The aim of this work consists on determining biomass fuels properties and studying their relation with fixed and variable costs of stores and handling systems. To do that, dimensions (length and diameter), bulk density, particle density and durability of several brands and batches of wood pellets and briquettes were tested, according to international standards. Obtained results were compared with those in literature. Bulk density tests were applied for several other biomass fuels too, and later used to determinate which ones of all the biomass-fuels tested are economically more profitable for a typical transport/store system made of a screw conveyor and a concrete bunker silo.


Some applications of the indium-113m-transferrin technique for gamma-radiation detection of microvascular effects of serotonin and ischemia.
The distribution of systematically injected In-113m (t1/2 = 100 min) in organs of the rat was analyzed, and the use of the isotope for in vivo and in vitro gamma-radiation detection studies of blood plasma protein extravasation was demonstrated in skin, muscle, and tumor. In-113m was slowly excreted from rats. One to 6 h after injection the blood held 3% and 2%, respectively, of injected radioactivity/g tissue wet weight; skin and muscle held 0.1%-0.2%/g; liver, colon, and spleen held approximately 1%/g; lungs 1.5%-1.3%/g and kidneys 2.8%-3.3%/g. Scintillation camera technique revealed 40%-80% extraaccumulation of In-113m in a control extremity upon local administration of serotonin and 20%-40% in an extremity with a transplanted tumor, thus indicating a lower effect of serotonin in tumor microvascular circulation than in muscle and skin. In vitro detection of In-113m radiation by a well-counter in dissected tissues showed no effects of serotonin in the tumor and a four- to five-fold increase of radioactivity in muscle and skin, thus confirming blood protein extravasation upon serotonin treatment in these tissues. External analyses of In-113m in the vascular system using one miniaturized probe directed toward an area of interest showed that the method was too sensitive to movements of the animal, and second probe directed toward a control area is needed.


A class I histone deacetylase is implicated in the encystation of Entamoeba invadens.
Epigenetic mechanisms such as histone acetylation and deacetylation participate in regulation of the genes involved in encystation of Entamoeba invadens. However, the histones and target residues involved, and whether the acetylation and deacetylation of the histones leads to the regulation of gene expression associated with the encystation of this parasite, remain unknown. In this study, we found that E. invadens histone H4 is acetylated in both stages of the parasite and is more highly acetylated during the trophozoite stage than in the cyst. Histone hyperacetylation induced by Trichostatin A negatively affects the encystation of E. invadens, and this inhibition is associated with the downregulation of the expression of genes implicated in the synthesis of chitin, polyamines, gamma-aminobutyric acid pathways and cyst wall proteins, all of which are important in the formation of cysts. Finally, in silico analysis and activity assays suggest that a class I histone deacetylase (EiHDAC3) could be involved in control of the expression of a subset of genes that are important in several pathways during encystation. Therefore, the identification of enzymes that acetylate and/or deacetylate histones that control encystation in E. invadens could be a promising therapeutic target for preventing transmission of other amoebic parasites such as E. histolytica, the causative agent of amoebiasis in humans.


Active case finding of pulmonary tuberculosis and HIV infection among prisoners of South Gujarat: A cross sectional study.
In a close knit congregation such as prison, Tuberculosis (TB) and HIV can be major health problems. However, their prevalence in Indian prisons is under reported. This study aimed at adopting a camp based, active case finding approach to identify cases of TB, HIV and at risk prisoners in a central prison of South Gujarat. A multidisciplinary team of public health experts, pulmonologists, social workers and lab technicians conducted a week-long camp to screen 1665 prisoners for TB using clinical examination, sputum smear for AFB, CBNAAT and Chest X-Ray and for HIV through Rapid Antigen Testing. Majority of participants (1392, 84%) were under trail prisoners, having spent an average of 1.4 years in prison. About 2.9% of participants had previous history of TB, of whom only 59% had completed treatment. About 14% of participants were underweight. Weight reduction was found to be significant in first five years of imprisonment. Of all participants, 3.6% were found to have diabetic range of blood sugar. Seven new active, drug sensitive pulmonary TB cases and three new cases of HIV infection were identified. All new cases of TB, HIV and increased blood sugar levels were linked to treatment. Camp based approach is effective in active case finding of pulmonary TB and predisposing factors such as malnourishment, Diabetes and HIV among prisoners. Routine screening of all prisoners at the time of entry and monthly thereafter in a camp based approach should be adopted to identify TB and at risk prisoners.


Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population.
Angiotensinogen (AGT) enzyme comprises a vital module of RAAS system that effectively controls the blood pressure and related cardiovascular functions. Ample association studies have reported the importance of AGT variants in cardiovascular and non-cardiovascular adversities. But lately, owing to the complexity of the many anomalies, the haplotype based examination of genetic variation that facilitates the identification of polymorphic sites which are located in the vicinity of the causative polymorphic site, gets greater appreciation. In the present study, we have done genotype and haplotype analysis of AGT gene in reference to hypertension to confirm the association of the two in an Indian population. To accomplish this, we performed candidate SNPs analysis and construct possible haplotypes across the AGT promoter and gene region in 414 subjects (256 Hypertensive cases and 158 controls). We found four SNPs (rs11568020: A-152G and rs5050: A-20C in promoter; rs4762 and rs699 in exon2) and 3 haplotypes (H4, H7 and H8) that showed a stronger positive association with hypertension. The haplotype H2 was showing protective association with hypertension. The results of the present study confirmed and reestablished the role of AGT gene variants and their haplotypes in the causation of hypertension in Indian population and showed that haplotypes can provide stronger evidence of association.


The relationship between media consumption and health-related anxieties after the Fukushima Daiichi nuclear disaster.
The Fukushima Daiichi nuclear disaster caused a global panic by a release of harmful radionuclides. In a disaster setting, misusage of contemporary media sources available today can lead to disseminated incorrect information and panic. The study aims to build a scale which examines associations between media and individual anxieties, and to propose effective media usages for future disaster management. The University of Tokyo collaborated with the Fukushima local government to conduct a radiation-health-seminar for a total of 1560 residents, at 12 different locations in Fukushima. A 13 item questionnaire collected once before and after a radiation-seminar was used on factor analysis to develop sub-scales for multiple regression models, to determine relationships between the sub-scales and media type consumed. A paired t-test was used to examine any changes in sub-scale of pre- and post-seminar scores. Three sub-scales were revealed and were associated with different media types: was with rumors, while concern for the future was positively associated with regional-newspapers and negatively with national-newspapers. Anxiety about social-disruption was associated with radio. The seminar had a significant effect on anxiety reduction for all the three sub-scales. Different media types were associated with various heightened concerns, and that a radiation seminar was helpful to reduce anxieties in the post-disaster setting. By tailoring post-disaster messages via specific media types, i.e., radio, it may be possible to effectively convey important information, as well as to calm fears about particular elements of post-disaster recovery and to combat rumors.


Long-term results after microsurgical repair of traumatic nerve lesions of the upper extremities.
Peripheral nerve injuries are still underestimated. This study examines the outcomes after surgical treatment of traumatic nerve lesions of the upper extremities. The different surgical techniques are analyzed with regard to the long-term outcome. This retrospective study presents the data of 93 patients (female: 24; male: 69) who were operated on for peripheral nerve injuries of the upper extremities in our department between 1991 and 2003. Mean age was 31 years (range, 5-67 years). Altogether 100 traumatic nerve lesions (ulnar nerve: 20; radial nerve: 22; median nerve: 25; axillary nerve: 6; accessory nerve: 7; musculocutaneous nerve: 2; long thoracic nerve: 1; digital nerve: 3; combined nerves: 7) were surgically treated. Surgical management included primary nerve suture in 16, neurolysis in 25, and nerve grafting in 59 patients. 74 patients (80%) were available for follow-up examination. The mean follow-up period was 35 months (range, 18-132 months). All patients up to the age of 20 years demonstrated good or excellent sensorimotor recovery. A good functional outcome was observed in 79% of the patients older than 20 years. Overall, good to excellent improvements of motor function were achieved for lesions of the musculocutaneous, radial, accessory and axillary nerves (100%, 89%, 100%, 100% functional useful muscle innervation, muscle recovery grade 3 and more). The length of grafts, in cases of secondary nerve reconstruction, did not influence functional outcome. Generally, early surgical repair of a nerve lesion predicted a better outcome. A good functional motor recovery was dependent on the age of the patient. Traumatic nerve lesions, without signs of reinnervation, should be treated surgically within a period of three months after injury.


Polymyxin susceptibility testing, interpretative breakpoints and resistance mechanisms: An update.
Emerging multidrug-resistant (MDR) nosocomial pathogens are a great threat. Polymyxins, an old class of cationic polypeptide antibiotic, are considered as last-resort drugs in treating infections caused by MDR Gram-negative bacteria. Increased use of polymyxins in treating critically ill patients necessitates routine polymyxin susceptibility testing. However, susceptibility testing both of colistin and polymyxin B (PMB) is challenging. In this review, currently available susceptibility testing methods are briefly discussed. The multicomponent composition of colistin and PMB significantly influences susceptibility testing. In addition, poor diffusion in the agar medium, adsorption to microtitre plates and the synergistic effect of the surfactant polysorbate 80 with polymyxins have a great impact on the performance of susceptibility testing methods This review also describes recently identified chromosomal resistance mechanisms, including modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose (L-Ara4-N) and phosphoethanolamine (pEtN) resulting in alteration of the negative charge, as well as the plasmid-mediated colistin resistance determinants mcr-1, mcr-1.2, mcr-2 and mcr-3.


Efficacy and Safety of Low-Molecular-Weight Heparin on Prevention of Venous Thromboembolism after Laparoscopic Operation for Gastrointestinal Malignancy in Japanese Patients: A Multicenter, Open-Label, Prospective, Randomized Controlled Trial.
The risk of venous thromboembolism (VTE) after surgery for malignancy in Japanese patients is unclear; therefore, standard prevention protocols have not been established, especially for minimally invasive procedures. We aimed to investigate the additional effect of low molecular weight heparin (LMWH) on prevention of VTE after laparoscopic surgery for gastrointestinal malignancy. From February 2013 to January 2017, 400 patients scheduled for laparoscopic surgery were included. Cases were randomly allocated to the physical therapy group (Control group; 201 patients) or to the combination-therapy group (LMWH group; 199 patients), in which enoxaparin sodium (20 mg [= 2000 IU] twice a day) was administered for 1 week postoperatively in addition to the physical therapy. A diagnosis of VTE was made by contrast-enhanced CT or ultrasonography when symptomatic or D-dimer was ≥10 μg/mL. VTE was observed in 1.2% and 4.0% of patients in the LMWH and Control groups, respectively (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.03-1.53). Pulmonary embolism was confirmed only in the Control group (1.7%). No major bleeding occurred in either group. Logistic multiple regression analysis revealed that surgical time extension (OR 1.02, 95% CI 1.00-1.04) was a risk factor of VTE, while administration of LMWH (OR 0.21, 95% CI 0.03-0.99), male sex (OR 0.12, 95% CI 0.01-0.60), and early cancer (OR 0.17, 95% CI 0.02-0.82) reduced the risk of VTE. Postoperative LMWH administration is safe. The additional effect of LMWH administration on the physical therapy was not statistically proven in this study. However, it could be useful for the patients with risk factors such as female sex, long operation time, and higher cancer stage.


Regulation of biosynthesis of secondary metabolites. XVII. Purification and properties of malate dehydrogenase (decarboxylating) in Streptomyces aureofaciens.
The process of isolation and purification of malate dehydrogenase (decarboxylating) (EC 126.96.36.199) from the mycelium of the actinomycete Streptomyces aureofaciens has been worked out. The enzyme was purified 35 fold. The kinetic characters of the purified enzyme are very similar to the figures for malate dehydrogenase (decarboxylating) from other sources. Km for L-malate = 2.1 X 10(-3)M, Km for NADP = 4.6 X 10(-5)M (at pH 7.4). The reaction requires metal divalent ions, Mn2+ being more effective than Mg2+. The enzyme reaches its maximal activity at pH 8.75.


Experimental and theoretical investigations on spectroscopic properties of the imidazole-fused phenanthroline and its derivatives.
Two phenanthroline derivatives, 1H-imidazo[4,5-f][1,10]phenanthroline (imPhen) and 2-(9H-fluoren-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (Flu-imPhen), have been synthesized and characterized and the corresponding absorption and emission spectroscopic properties have been studied in CH2Cl2 solution. The imPhen exhibits the main two absorption bands at 282 nm and 229 nm and these bands are assigned as the typical π→π*(Phen) state. In addition, the weak absorption bands at 313 nm associated with a shoulder near 302 nm were assigned to the π→π*(Phen) state with partial charge transfer (CT) character. A similar absorption spectra are observed in the case of the Flu-imPhen in the region of 200-300 nm, while the region of 300-400 nm of the spectra are dominated by the characteristic π→π* transition of the fluorene moiety. imPhen shows the typical ligand-centered (1)π→π* emission, while Flu-imPhen emits from the mixed (1)π→π*/CT states. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) were employed to rationalize the photophysical properties of these ligands studied. The theoretical data confirm the assignment of the experimental absorption spectra and the nature of the emitting states.


The clinical significance of diffusion-weighted MR imaging in infratentorial strokes.
To study the association between diffusion-weighted imaging (DWI) characteristics and stroke etiology, stroke severity, and functional outcome in patients with infratentorial strokes. The authors prospectively studied 22 consecutive patients with acute infratentorial strokes. They used a blinded comparison of DWI features (number, distribution, and volume of lesions) with clinical characteristics, namely, stroke etiology (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), severity (NIH Stroke Scale [NIHSS]), length of stay (LOS), and functional 3-month outcome using modified Rankin Scale, Barthel Index, and a dichotomized outcome status (living at home vs institutionalization or death). Acute infratentorial DWI lesions were detected in 95% (21/22) of the patients. The number (p = 0.01) and the distribution (p < 0.001) of DWI lesions were correlated with stroke etiology. Patients with cardioembolic strokes (n = 5) had more DWI lesions (8.0 +/- 6.0) than those with other stroke etiologies (n = 17; 1.3 +/- 0.9; p < 0.001). Their lesion distribution differed from that of patients with noncardioembolic strokes (p < 0.001). Clinically silent, acute DWI lesions in the anterior circulation in addition to their infratentorial lesions were visualized in 3 of 5 patients with cardioembolic stroke and in none of 17 patients without sources of cardioembolism (p < 0.001). Pure infratentorial lesions were present in 15 of 17 patients with noncardioembolic strokes and in none of 5 cardioembolic stroke patients (p < 0.001). DWI lesion volume was not correlated with NIHSS score, LOS, outcome scores, or outcome status. In infratentorial strokes, multiple DWI lesions and a distribution of subsidiary, clinically silent DWI lesions in the anterior circulation suggest a cardioembolic stroke etiology. However, DWI lesion volume did not correlate with the NIHSS score and was no predictor of outcome.


Formation of odorous aldehydes, nitriles and N-chloroaldimines from free and combined leucine during chloramination.
Amino acids (AAs) are a major group of odorous disinfection by-product (O-DBP) precursors. O-DBPs formations during free chlorine disinfection has been previously investigated. However, knowledge regarding the O-DBP formation mechanism and kinetics under chloramination of AAs is very limited. In this study, the generation of odorous isovaleraldehyde, isovaleronitrile and N-chloroisovaleraldimine from leucine (Leu), a typical and abundant AA in many drinking water sources, in its free and combined forms during chloramination under several typical addition schemes of disinfectants was investigated. Free Leu and glycylleucine (Gly-Leu) were chosen as model compounds since they have been indicated to be O-DBP precursors during chlorination. Intermediate product analysis and kinetics studies were conducted to study the reaction mechanisms. Impacts of disinfectants dosages and pH were also investigated in experiments and simulations. The results indicated that comparing with chlorination, chloramination of Leu has its uniqueness by participating in reacting with isovaleraldehyde to form N-chloroisovaleraldimine. And all the three O-DBPs formations from free Leu and Gly-Leu during chloramination (with preformed NH2Cl) were less than those during chlorination, indicating that using NH2Cl for disinfection ensures control over the off-flavor problems to some degree. When chloramination was realized by adding chlorine and ammonia separately, a longer pre-chlorination time led to greater yields of the O-DBPs from both precursors, whereas adding ammonia before chlorine promoted more isovaleraldehyde formation from free Leu. Under alkaline conditions, more isovaleronitrile and N-chloroisovaleraldimine were produced, and acidic conditions led to more isovaleraldehyde formation during chloramination. Notably, O-DBPs yields from free Leu were approximately 1000 times greater than those from Gly-Leu during chloramination under all the schemes. In addition, chlor(am)ination experiments with real water from Taihu Lake (the third largest freshwater lake and water source for twenty million people in China) indicated the formation of N-chloroisovaleraldimine and isovaleraldehyde was highly likely to cause odorous problems in drinking water. This study facilitates further understanding of the causes of off-flavor issues in drinking water and can help control the odorous problems by optimizing the operating parameters of drinking water treatment plants.


Activation of valvular interstitial cells is mediated by transforming growth factor-beta1 interactions with matrix molecules.
Strategies for the tissue-engineering of living cardiac valve replacements are limited by a lack of appropriate scaffold materials that both permit cell viability and actively contribute to the growth of functional tissues. Components of the extracellular matrix can localize and modify growth factor signals, and by doing so impart instructional stimuli for direction of cell phenotype. Fibronectin, collagen I, and heparin were explored as affinity matrices for sequestering and presenting soluble signaling molecules to control differentiation of valvular interstitial cells (VICs) to myofibroblasts. VIC differentiation is commonly characterized by expression of stress fibers containing alpha smooth muscle actin (alpha-SMA), and transforming growth factor-beta1 (TGF-beta1) is a central mediator of this transition. Both fibronectin and heparin, which are known to possess TGF-beta1 binding interactions, were found to increase VIC alpha-SMA expression (120% and 258% of expression in controls), while VICs cultured on collagen I-modified substrates had diminished alpha-SMA expression (66% of control). Heparin treatment significantly stimulated VIC production of TGF-beta1 at all concentrations tested (50 to 400 mug/ml). Heparin-modified substrates were found to alter cell morphology through increased adsorption of serum proteins, specifically TGF-beta1. In sum, heparin produced alpha-SMA-positive myofibroblasts through both the de novo production of TGF-beta1, and its localization in the pericellular environment. The addition of heparin to fibronectin-modified substrates led to a synergistic increase in VIC alpha-SMA expression, produced by the reciprocal binding of fibronectin, heparin, cell-produced TGF-beta1. The characterization of molecules, both soluble and insoluble, that control VIC activation will be important for the development of tailored 3D culture environments for tissue-engineering applications.


Environmental hazard of cationic polymers relevant in personal and consumer care products: A critical review.
Historically, polymers have been excluded from registration and evaluation under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program, the European chemical management program. Recently, interest has increased to include polymers. A tiered registration system has been envisioned and would begin with classes of polymers of greater interest based on certain properties. Cationic polymers are one such class. There is a pressing need to understand the quality and limitations of historical cationic polymer studies and to identify key sources of uncertainty in environmental hazard assessments so we can move toward scientifically robust analyses. To that end, we performed a critical review of the existing cationic polymer environmental effects literature to evaluate polymer characterization and test methodologies to understand how these parameters may affect test interpretation. The relationship between physicochemical parameters, acute and chronic toxicity, and relative trophic level sensitivity were explored. To advance our understanding of the environmental hazard and subsequent risk characterization of cationic polymers, there is a clear need for a consistent testing approach as many polymers are characterized as difficult-to-test substances. Experimental parameters such as dissolved organic carbon and solution renewal approaches can alter cationic polymer bioavailability and toxicity. It is recommended that OECD TG 23 "Aqueous-Phase Aquatic Toxicity Testing of Difficult Test Substances" testing considerations be applied when conducting environmental toxicity assays with cationic polymers. Integr Environ Assess Manag 2023;19:312-325. © 2021 SETAC.


Running Performance, VO2max, and Running Economy: The Widespread Issue of Endogenous Selection Bias.
Studies in sport and exercise medicine routinely use samples of highly trained individuals in order to understand what characterizes elite endurance performance, such as running economy and maximal oxygen uptake VO2max. However, it is not well understood in the literature that using such samples most certainly leads to biased findings and accordingly potentially erroneous conclusions because of endogenous selection bias. In this paper, I review the current literature on running economy and VO2max, and discuss the literature in light of endogenous selection bias. I demonstrate that the results in a large part of the literature may be misleading, and provide some practical suggestions as to how future studies may alleviate endogenous selection bias.


How Frequent is the One-Hour tPA Infusion Interrupted or Delayed?
Tissue plasminogen activator (tPA) requires a one-hour infusion after the bolus. The frequency of delay or interruption of the tPA infusion may be useful in weighing the advantages of Tenecteplase (TNKase, TNK) which does not require an infusion. Utilizing the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services study database, we calculated the frequency and magnitude of tPA infusion delay or interruption. Of 497 patients treated with tPA on the Houston Mobile Stroke Unit (MSU), 41 (8.3%) had delay or interruption of the infusion for reasons that did not reflect a side effect of, or contraindication to, tPA. Nine received less than 90% of their calculated dose (median 62%, range 28-88%), and eleven had more than a 10% prolongation of their infusion (median 19 min, range 7-210 min). Six patients (1.2%) had infusion stopped for a valid concern for tPA side effect or contraindication. Interruption or discontinuation of the tPA infusion occurs in 8% of patients treated on a MSU providing an opportunity for more complete and faster treatment with TNK.


Chrysotile asbestos is progressively converted into a non-fibrous amorphous material by the chelating action of lichen metabolites.
A natural deactivation of chrysotile asbestos occurs on serpentinite rocks where lichens selectively grow on the fibres and secrete metabolites, including oxalic acid, which, in the long term, turn the fibres into a non-toxic amorphous material.


Serotype distribution and penicillin-non-susceptibility of Streptococcus pneumoniae causing invasive diseases in Kuwait: A 10-year study of impact of pneumococcal conjugate vaccines.
The impact of PCV7 and PCV13 on pneumococcal infections in Kuwait is not known. Therefore we evaluated the impact on pneumococcal serotype distribution and penicillin-non-susceptibility in invasive infections in Kuwait. Children < 2 y were given PCV7 from Aug 2006 to Jul 2010 (period I), and PCV13 from Aug 2010 to Jul 2013 (period II) with a pre-vaccination period from Aug 2003 to Jul 2006. Serotype and penicillin-non-susceptibility of blood and cerebrospinal fluid isolates from all ages were determined. In <2 y old children, even with a small number of infections, a drop in PCV7 serotypes was evident after vaccination. For all age groups combined, in the pre-vaccination period, PCV7, PCV13, PCV13 non-PCV7 serotypes and penicillin-non-susceptibility constituted 53.2%, 72.6%, 19.4% and 6.5% of the isolates respectively. PCV7, PCV13 non-PCV7 serotypes and penicillin-non-susceptibility changed to 32.7%, 28.2% and 7.3% (period I) and 6.6%, 22.2% and 8.9% (period II). Vaccines reduced invasive infections due to PCV7 serotypes.


Weight loss and metabolic improvements in obese patients undergoing gastric banding and gastric banded plication: A comparison.
Obesity is a pandemic health problem. Bariatric surgery is the only efficient method for long-term effective weight loss in subjects with severe obesity. Laparoscopic adjustable gastric banding (LAGB) has been widely applied for weight loss. However, a novel technique called laparoscopic adjustable gastric banded plication (LAGBP) has been proposed as an alternative to LAGB. Surgeons generally consider LAGBP to have a relative advantage on weight loss than that derived from LAGB. This initial study applied various biostatistical models and considered a relative longer observation period to compare the effects of LAGB and LAGBP. A total of 340 obese patients (290 who underwent LAGB and 50 who underwent LAGBP) with a body mass index of ≥35 kg/m2 and ages 20 to 55 y were recruited from the Division of General Surgery, Taipei Medical University Hospital in Taipei, Taiwan and observed for 24 to 36 mo postoperatively. Both surgical procedures resulted in significant weight loss, amelioration of poor glucose metabolism, and decreased serum triacylglycerol levels. However, the trend analysis showed no significant differences between the postoperative effects of LAGB and LAGBP (P for trend = 0.21 for body mass index reduction, 0.13 for total body fat percentage reduction, 0.25-0.29 for glucose metabolism amelioration, and 0.10-0.29 for blood pressure improvement). Improvements in serum total cholesterol and high-density lipoprotein cholesterol levels were observed after LAGB only and LAGBP only, respectively, at 24 mo postoperatively. The Framingham Coronary Heart Disease Risk score also showed significant decrease for patients who underwent LAGB and LAGBP. Both LAGB and LAGBP demonstrated comparable efficacy in reducing body weight and improving metabolic parameters in a 24 to 36 mo follow-up period. LABG showed the ability to reduce systolic blood pressure and LAGBP exhibited triacylglycerol-lowering effects. A longer observational period is needed in future studies.


[Comparative study of superoxide dismutase and glutathione peroxidase activity in embryos and skeletal muscles of adult fish].
The activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase in loach and sturgeon embryogenesis as well as in red and white skeletal muscles of loach was studied. The specific activity of cytoplasmic and mitochondrial forms of superoxide dismutase in developing sturgeon embryos was higher than in loach embryos, which may be due to oxygen conditions under which these species develop in nature. A similar dependence was also observed for the activity of glutathione peroxidase in embryos of these fish species. A comparative study of specific superoxide dismutase activity in loach and sturgeon embryos and in loach skeletal muscles showed that the activity of cytoplasmic superoxide dismutase is maximum in red and white muscles and minimum in loach embryos, whereas the activity of the mitochondrial form of this enzyme is maximum in red skeletal muscles.


Selection algorithm for posterior versus lateral approach in laparoscopic adrenalectomy.
There are no objective selection criteria described in the literature for the laparoscopic posterior retroperitoneal (PR) versus lateral transabdominal (LT) approach in a given patient. The aim of this study is to quantify the algorithm we have been using in our practice. Within 11 years, 219 patients underwent laparoscopic adrenalectomy at one institution. The laparoscopic LT technique was used in patients with unilateral tumors >6 cm. In those patients with unilateral tumors <6 cm, anthropometric parameters were used to select between laparoscopic PR and LT approaches. These parameters were quantified for 82 patients from computed tomography scans and their effects on operative time were calculated. Statistical analyses were performed by use of the t test and logistic regression analysis. Fifty-two patients underwent laparoscopic LT and 30 patients underwent PR adrenalectomy. Patients were selected for the PR approach if the distance from Gerota's fascia to the skin was less than 5 cm and the 12th rib was at or rostral to the level of renal hilum. On multivariate analysis, total operative time correlated with body mass index in the LT approach and thickness of the perinephric fat and the distance between the adrenal tumor and the upper pole of kidney in the PR approach. In this study, we have described an objective algorithm that can be used to select patients with unilateral adrenal tumors <6 cm for a laparoscopic PR or LT approach with favorable perioperative outcomes.


Tumor-associated metabolism in the rat is a unique physiologic entity.
The metabolic responses associated with the tumor-bearing state, as compared to states of sepsis and prolonged starvation, were examined. Tumor-bearing rats manifested significant elevation of triglycerides, significant reduction of glucose and insulin levels, significantly increased plasma skeletal muscle proteolysis-inducing activity, and an unchanged hepatic protein synthetic activity compared to control rats. Prolonged starvation produced an adaptation characterized by significant hypoglycemia and hypoinsulinemia, reduced hepatic protein synthesis, and increased peripheral protolysis compared to controls. Septic animals had glucose, insulin, and lipid levels similar to control animals but had increased hepatic protein synthesis. Each state manifested its own unique metabolic response compared to controls. It appears that the metabolic consequences of cancer in this sarcoma rat model is different than septic and prolonged starvation states.


Variation of glutamate decarboxylase activity and gamma-amino butyric acid content of wheat embryos during ripening of seeds.
GAD activity and gamma-ABA content of wheat embryos at 7 ripening stages were verified with the aim of studying the metabolic activity of embryo during dehydration and quiescence of caryopsis. Data showed that in the early stage of ripening GAD activity is very low, increases rapidly at dough-stage, remaining constant up to waxy-stage, and decreases in the last fully-ripe embryos. gamma-ABA content appears to be roughly parallel to the variations of GAD activity.


An event-related fMRI investigation of phonological-lexical competition.
This study explored the neural correlates of phonological-lexical competition and frequency on word recognition. An event-related fMRI experiment was conducted using an auditory lexical decision task in which word and nonword stimuli varied in terms of neighborhood density (high and low). Word stimuli also varied in terms of frequency (high and low). Behavioral results were similar to those of Luce and Pisoni [Luce, P. A., & Pisoni, D. B. (1998). Recognizing spoken words: The neighborhood activation model. Ear and Hearing, 19, 1-36], with the reaction time data showing a main effect of word frequency and density as well as a significant interaction effect between these two factors. fMRI results revealed an overall greater neural response for high-density compared to low-density words in the left supramarginal gyrus, consistent with the view that there are greater demands on phonological processing under conditions of increased phonological-lexical competition. The comparison between high and low frequency words revealed greater activation for high frequency words in both anterior and posterior left middle temporal gyrus. A significant interaction between density and frequency was found in lateral and medial frontal structures. This frontal activation may reflect the greater computational resources required in integrating frequency and density information in order to access a word. Overall, these findings demonstrate the sensitivity of neural structures to different properties of the lexicon.


Investigation of LED-based photodynamic therapy efficiency on breast cancer cells.
Photodynamic therapy (PDT) is based on special light source, photosensitizer (PS), and in the presence of oxygen. Different light sources have been used for PDT applications. Recent studies have focused on LED light sources for PDT applications due to reducing the cost of laser-based PDT and providing easy access for research laboratory or clinic facilities. LED-mediated PDT applications have shown promising results for the treatment of different types of disease. However, few studies have determined the effects of LED-based PDT on cancer cells. For the first time, the aim of this study was to explore the therapeutic effects of 5-aminolevulinic acid (5-ALA)-mediated PDT after LED irradiation on two sub-types (a poorly aggressive MCF-7 and a highly aggressive MDA-MB-231) of breast cancer cell lines. The effectiveness of 5-ALA PDT treatment was evaluated by WST-1, annexin V, and acridine orange staining with different energy levels. The LED system was specially developed with optical power and wavelength stability techniques. The system consists of user interface and embedded LED controller with real-time optic power output calibration by photodiode feedback. Our results demonstrated that the cell viability of breast cancer cells was considerably decreased a LED dose-dependent manner (P < 0.05). Additionally, a significant increase in the percentage of apoptotic cells was detected in breast cancer cells after irradiation with LED at a density of 18 and 30 J/cm2 energy. Consequently, the LED system could be effectively used for irradiation of 5-ALA in the treatment of breast cancer cells.


Compliance with an oral hyperproteic supplement with fibre in nursing home residents.
Undernutrition is a common problem in older individuals that may be related to a low protein dietary intake. Oral supplements may improve the health status in this population, but their use may be limited by compliance and side effects. To evaluate effects of an oral supplement of protein and fibre on compliance, on nutritional status, and on intestinal habits in nursing home residents. A prospective observational study was carried out in 66 Spanish nursing homes. 358 subjects undernourished or at risk of undernutrition requiring nutritional supplements. After informed consent was given, subjects received 2 daily cartons (400 ml) of a liquid oral supplement rich in protein and fibre along 3 months. Supplement intake compliance was measured at baseline and after 6 and 12 weeks. Nutritional status was assessed using the Mini- Nutritional Assessment (MNA), weight, and Body Mass Index (BMI). Changes in intestinal habits and digestive symptoms were also recorded, as well as subject's supplement acceptance. Compliance with the supplement intake was 97.46% at 6 weeks and 96% at 12 weeks of follow-up. Significant changes (p<0.0001) were found in nutritional status: mean value of MNA improved from baseline (MNA=14.0+/-3.9) after 12 weeks (MNA=17.0+/-4.0), as well as weight (+2.1 kg, a 4.1% increase). The BMI did not change significantly (BMI=21.43 at baseline; BMI=21.78 at 12 weeks). Undernutrition prevalence (MNA<17) decreased from 76.4 to 46.6% (p<0.0001). Intestinal habits showed a significant improvement in defecation frequency (from 4.7 to 6.1 stools per week, p<0.0001) and faeces consistency (from 53.2% to 74.5% reporting formed soft stools, p<0.0001). 48.9% of the subjects considered to have better intestinal habits after 6 weeks and 50.5% after 3 months of supplementary food intake, the rest reporting no change. Vomits and flatulence were also significantly reduced (p<0.0001). The administration of an oral hyperproteic supplement with fibre in aged subjects who are undernourished or at risk of malnutrition can be done in nursing homes with a high level of compliance. Supplements improve their nutritional status and their intestinal habits.


Neurexophilin 1 gene polymorphism in chickens and its variation among species.
Neurexophilin 1 (nxph1) has been considered a potential candidate marker for sperm storage in chicken sperm storage tubules. In this work, one mutation of chicken nxph1 was detected. We analyzed 18 nxph1 gene sequences from 18 species. The coding sequence length of the zebra fish nxph1 gene is 819 bp; that of the other species is 816 bp. Amino acid alignment analysis revealed that the gene product is a conserved protein, especially in mammals. The sequences of mammals are highly conserved. We found 202 conserved amino acids (70-271), and there were only eight mutations in the remaining 69 amino acids. That level of conservation could be due to the nxph1 gene having been subjected to substantial constraints or strong purifying selection during millions of years of evolution.


Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions.
Reconstruction of the evolution of start codons in 36 groups of closely related bacterial and archaeal genomes reveals purifying selection affecting AUG codons. The AUG starts are replaced by GUG and especially UUG significantly less frequently than expected under the neutral expectation derived from the frequencies of the respective nucleotide triplet substitutions in non-coding regions and in 4-fold degenerate sites. Thus, AUG is the optimal start codon that is actively maintained by purifying selection. However, purifying selection on start codons is significantly weaker than the selection on the same codons in coding sequences, although the switches between the codons result in conservative amino acid substitutions. The only exception is the AUG to UUG switch that is strongly selected against among start codons. Selection on start codons is most pronounced in evolutionarily conserved, highly expressed genes. Mutation of the start codon to a sub-optimal form (GUG or UUG) tends to be compensated by mutations in the Shine-Dalgarno sequence towards a stronger translation initiation signal. Together, all these findings indicate that in prokaryotes, translation start signals are subject to weak but significant selection for maximization of initiation rate and, consequently, protein production.


Circulating mannose-binding lectin concentration in patients with stable coronary artery disease is associated with heart failure and renal function.
Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60-89 and 15-59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01-3.55) times and 2.37 (1.25-4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01-3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure.


Carbon dioxide laser fabrication of fused-fiber couplers and tapers.
We report the development of a fiber taper and fused-fiber coupler fabrication rig that uses a scanning, focused, CO(2) laser beam as the heat source. As a result of the pointlike heat source and the versatility associated with scanning, tapers of any transition shape and uniform taper waist can be produced. Tapers with both a linear shape and an exponential transition shape were measured. The taper waist uniformity was measured and shown to be better than +/-1.2%. The rig was also used to make fused-fiber couplers. Couplers with excess loss below -0.1 dB were routinely produced.


Temporal Dynamics of Metabolic Acquisition in Grafted Engineered Human Liver Tissue.
Liver disease affects millions globally, and end-stage liver failure is only cured by organ transplant. Unfortunately, there is a growing shortage of donor organs as well as inequitable access to transplants across populations. Engineered liver tissue grafts that supplement or replace native organ function can address this challenge. While engineered liver tissues have been successfully engrafted previously, the extent to which these tissues express human liver metabolic genes and proteins remains unknown. Here, it is built engineered human liver tissues and characterized their engraftment, expansion, and metabolic phenotype at sequential stages post-implantation by RNA sequencing, histology, and host serology. Expression of metabolic genes is observed at weeks 1-2, followed by the cellular organization into hepatic cords by weeks 4-9.5. Furthermore, grafted engineered tissues exhibited progressive spatially restricted expression of critical functional proteins known to be zonated in the native human liver. This is the first report of engineered human liver tissue zonation after implantation in vivo, which can have important translational implications for this field.


Fronto-medial theta coordinates posterior maintenance of working memory content.
How does the human brain manage multiple bits of information to guide goal-directed behavior? Successful working memory (WM) functioning has consistently been linked to oscillatory power in the theta frequency band (4-8 Hz) over fronto-medial cortex (fronto-medial theta [FMT]). Specifically, FMT is thought to reflect the mechanism of an executive sub-system that coordinates maintenance of memory contents in posterior regions. However, direct evidence for the role of FMT in controlling specific WM content is lacking. Here, we collected high-density electroencephalography (EEG) data while participants engaged in WM-dependent tasks and then used multivariate decoding methods to examine WM content during the maintenance period. Engagement of WM was accompanied by a focal increase in FMT. Importantly, decoding of WM content was driven by posterior sites, which, in turn, showed increased functional theta coupling with fronto-medial channels. Finally, we observed a significant slowing of FMT frequency with increasing WM load, consistent with the hypothesized broadening of a theta "duty cycle" to accommodate additional WM items. Together, these findings demonstrate that frontal theta orchestrates posterior maintenance of WM content. Moreover, the observed frequency slowing elucidates the function of FMT oscillations by specifically supporting phase-coding accounts of WM.


Toxicological and pharmacological investigations of pinazepam (7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one): a new psychotherapeutic agent.
The pharmacological and toxicological properties of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) were investigated and compared with those of diazepam. In mouse and rat acute toxicity, in rat motor coordination and in rat metrazol convulsion tests pinazepam was compared with oxazepam too. Pinazepam, which is characterized by the presence of a propargylic side chain, showed a lower toxicity, hypnotic activity and muscular-relaxant activity than diazepam. Pinazepam and diazepam showed, however, similar activity in reducing aggressive behaviour in mice, stimulating the exploratory behaviour in rats and in potentiating hexobarbital narcosis. No clear-cut differences were observed in the anticonvulsant properties of the two drugs when tested against metrazol, strychnine and electroshock induced seizures. Pinazepam differs from diazepam for its longer duration of action. The main metabolic product found in the urine of rats and dogs treated with pinazepam was oxazepam.


Central motor conduction times using transcranial stimulation and F wave latencies.
The purpose of this study was to determine central motor conduction times between the motor cortex and the C8 spinal cord level (MC/C8), the motor cortex and S1 cord level (MC/S1), and C8 and S1 (C8/S1). We stimulated 29 normal subjects with a transcranial high voltage (300-500 V), short duration spike waveform (time constant 50 mu sec) and recorded over the hypothenar or calf muscles. F wave and M response latencies were used to estimate peripheral conduction time. The mean MC/C8 conduction time was 4.4 +/- 0.6 msec. Out of 26 subjects tested, 14 had discernable responses in the calf. The mean MC/S1 conduction time was 13.1 +/- 2.5 msec, and the mean estimated C8/S1 conduction time was 8.5 +/- 2.3 msec. This technique accurately measures conduction time from the motor cortex to the cervical anterior horn cells but is less reliable for monitoring conduction to the sacral cord. These values will facilitate future studies in patients with suspected lesions of the descending motor pathways.


RT-PCR and sequence analysis of the full-length fusion protein of Canine Distemper Virus from domestic dogs.
During 2007-2014, 84 out of 236 (35.6%) samples from domestic dogs submitted to our laboratory for diagnostic purposes were positive for Canine Distemper Virus (CDV), as analyzed by RT-PCR amplification of a fragment of the nucleoprotein gene. Fifty-nine of them (70.2%) were from dogs that had been vaccinated against CDV. The full-length gene encoding the Fusion (F) protein of fifteen isolates was sequenced and compared with that of those of other CDVs, including wild-type and vaccine strains. Phylogenetic analysis using the F gene full-length sequences grouped all the Argentinean CDV strains in the SA2 clade. Sequence identity with the Onderstepoort vaccine strain was 89.0-90.6%, and the highest divergence was found in the 135 amino acids corresponding to the F protein signal-peptide, Fsp (64.4-66.7% identity). In contrast, this region was highly conserved among the local strains (94.1-100% identity). One extra putative N-glycosylation site was identified in the F gene of CDV Argentinean strains with respect to the vaccine strain. The present report is the first to analyze full-length F protein sequences of CDV strains circulating in Argentina, and contributes to the knowledge of molecular epidemiology of CDV, which may help in understanding future disease outbreaks.


Data on polymorphisms in CYP2A6 associated to risk and predispose to smoking related variables.
This article contains data on the single nucleotide polymorphisms (SNPs) rs1137115, rs1801272 and rs28399433 rs4105144 in CYP2A6 associated to smoking related variables in Mexican Mestizo smokers (Pérez-Rubio et al., 2017) [1]. These SNPs were selected due to previous associations with other populations. Mexican Mestizo smokers were classified according their smoking pattern. A genetic association test was performed.


Reversible myopathy during successful treatment with pegylated interferon and ribavirin for acute hepatitis C.
There is no standard approved treatment for acute hepatitis C and the combination of pegylated interferon-alpha and ribavirin, currently recognized as the standard of care for chronic hepatitis C, has not been evaluated for acute hepatitis C. Adverse events induced by interferon therapy are numerous but myopathy is rare and has not been described with the use of pegylated interferon-alpha. We report the case of a 33-year-old Caucasian man who was successfully treated for acute hepatitis C with the combination of pegylated interferon-alpha2b and ribavirin, and who during treatment developed myopathy which proved reversible.


The effect of selected amino acids on gelatin-induced inflammation in adult male mice.
Several studies have indicated to us that certain amino acids may exhibit antiinflammatory activity. In the present study we attempted to evaluate the inhibitory effect of various amino acids on gelatin-induced abdominal inflammation in mice using peritoneal fluid cytology as the diagnostic tool. The L-amino acids tested were tryptophan, phenylalanine, alanine, cystine, hydroxyproline, tyrosine, citrulline, leucine, and valine. Hydrocortisone was used as an antiphlogistic steroid control. Tryptophan, phenylalanine, alanine, cystine, hydroxyproline, and tyrosine all significantly decreased the inflammation. Citrulline and valine, however, both exhibited strong antiiflammatory responses. Based on these results, three related dipeptides were also screened: L-valy-L-alanine, L-valyl-L-tryptophan, and L-tyrosl-L-valine. Valyl alanine was found to produce a strong antiinflammatory effect. In a final test, the combination of the steroid, hydrocortisone, and the amino acid, cystine, was screened for a synergistic effect. The combined treatment inhibited the gelatin-induced inflammation more than either the amino acid or the steroid administered alone.


Screen of high efficiency cellulose degrading strains and effects on tea residues dietary fiber modification: Structural properties and adsorption capacities.
In our study, two high efficiency cellulose degrading strains were screened, isolated and identified as Cochliobolus kusanoi and Aspergillus puulaauensis by 18S rDNA gene sequencing. In addition, the composite microbial system was constructed to develop the synergistic effect among different strains. Under the optimum conditions, the yield of soluble dietary fiber from tea residues by mixed fermentation method (MF-SDF) dramatically increased compared to single strain fermentation. The structural analysis demonstrated that all samples possessed the representative infrared absorption peaks of polysaccharides, whereas MF-SDF revealed more loose structure, lower crystallinity and smaller molecular size. For the adsorption capacities indexes, MF-SDF also owned the highest adsorbing capacity for the water molecule, oil molecule, cholesterol molecule and nitrite ion. Overall, our data showed that mixed fermentation method could be better choices to improve the functional properties of dietary fiber, and screening of cellulose degrading strains could provide new thinkings for the study of dietary fiber modification and realize high-quality utilization of crop residues.


Relationship between cycles in level of serotonin N-acetyltransferase activity and cyclic GMP content of cultured chick pineal glands.
We examined effects of supplements on cycles in cyclic GMP content and serotonin N-acetyltransferase (NAT) activity in cultured chick pineal glands. Increases in cyclic GMP content and NAT activity were stimulated by 1-ethyl-4(isopropylidene-hydrazino)-1H-pyrazolo[3,4-b]pyridene-5-c arboxylic acid, ethyl ester, hydrochloride and isobutylmethyl xanthine under diurnal illumination and in constant darkness, but subsequent decreases were not inhibited. Hypoxanthine had little effect on NAT activity under all lighting conditions, or on the content of cyclic GMP in glands cultured in the dark. However, it markedly stimulated accumulation of cyclic GMP in illuminated cultures. EGTA or additional Ca2+ had no effect on pineal NAT activity. However, EGTA markedly stimulated accumulation of cyclic GMP both in the light and in the dark. Supplementary Ca2+ slightly retarded accumulation of cyclic GMP in the dark but stimulated slightly in the light.


Nutritional Aspects of Dysphagia Management.
This chapter describes the nutritional aspects of dysphagia management by starting with the definition of these two conditions (dysphagia and malnutrition) that share three main clinical characteristics: (a) their prevalence is very high, (b) they can lead to severe complications, and (c) they are frequently underrecognized and neglected conditions. From an anatomical standpoint, dysphagia can result from oropharyngeal and/or esophageal causes; from a pathophysiological perspective, dysphagia can be caused by organic or structural diseases (either benign or malignant) or diseases causing impaired physiology (mainly motility and/or perception disorders). This chapter gathers up-to-date information on the screening and diagnosis of oropharyngeal dysphagia, the consequences of dysphagia (aspiration pneumonia, malnutrition, and dehydration), and on the nutritional management of dysphagic patients. Concerning this last topic, this chapter reviews the rheological aspects of swallowing and dysphagia (including shear and elongational flows) and its influence on the characteristics of the enteral nutrition for dysphagia management (solid/semisolid foods and thickened liquids; ready-to-use oral nutritional supplements and thickening powders), with special focus on the real characteristics of the bolus after mixing with human saliva.


TIGIT blockade enhances NK cell activity against autologous HIV-1-infected CD4+ T cells.
During chronic human immunodeficiency virus (HIV)-1 infection, inhibitory molecules upregulated on lymphocytes contribute to effector cell dysfunction and immune exhaustion. People living with HIV (PLWH) are at greater risk for age-related morbidities, an issue magnified by human cytomegalovirus (CMV) coinfection. As CMV infection modifies natural killer (NK) cell properties and NK cells contribute to protection against HIV-1 infection, we considered the role of T-cell immunoreceptor with immunoglobulin and intracellular tyrosine inhibitory motif domains (TIGIT) in NK cell-based HIV-1 immunotherapy and elimination strategies. We measured TIGIT expression on immune cell subsets of 95 PLWH and assessed its impact on NK cell function, including elimination of autologous CD4+ T cells infected through reactivation of endogenous HIV-1. TIGIT was expressed on CD4+ T cells, CD8+ T cells and NK cells from PLWH. Although TIGIT levels on T cells correlated with HIV-1 disease progression, the extent of TIGIT expression on NK cells more closely paralleled adaptation to CMV. TIGIT interacts with its predominant ligand, poliovirus receptor (PVR), to inhibit effector cell functions. Circulating CD4+ T cells from PLWH more frequently expressed PVR than HIV-seronegative controls, and PVR expression was enriched in CD4+ T cells replicating HIV-1 ex vivo. Treatment with anti-TIGIT monoclonal antibodies increased NK cell HIV-1-specific antibody-dependent cytotoxicity in vitro and ex vivo. Blocking TIGIT may be an effective strategy to invigorate antibody-dependent NK cell activity against HIV-1 activated in cellular reservoirs for cure or treatment strategies.


Proteomic Mapping of the Interactome of KRAS Mutants Identifies New Features of RAS Signalling Networks and the Mechanism of Action of Sotorasib.
RAS proteins are key regulators of cell signalling and control different cell functions including cell proliferation, differentiation, and cell death. Point mutations in the genes of this family are common, particularly in KRAS. These mutations were thought to cause the constitutive activation of KRAS, but recent findings showed that some mutants can cycle between active and inactive states. This observation, together with the development of covalent KRASG12C inhibitors, has led to the arrival of KRAS inhibitors in the clinic. However, most patients develop resistance to these targeted therapies, and we lack effective treatments for other KRAS mutants. To accelerate the development of RAS targeting therapies, we need to fully characterise the molecular mechanisms governing KRAS signalling networks and determine what differentiates the signalling downstream of the KRAS mutants. Here we have used affinity purification mass-spectrometry proteomics to characterise the interactome of KRAS wild-type and three KRAS mutants. Bioinformatic analysis associated with experimental validation allows us to map the signalling network mediated by the different KRAS proteins. Using this approach, we characterised how the interactome of KRAS wild-type and mutants is regulated by the clinically approved KRASG12C inhibitor Sotorasib. In addition, we identified novel crosstalks between KRAS and its effector pathways including the AKT and JAK-STAT signalling modules.


Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia.
Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0-18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.


Estrogen receptor ligands. Part 1: The discovery of flavanoids with subtype selectivity.
A class of flavanoids exhibiting a high degree of selectivity for ERalpha over ERbeta has been discovered. The most active analogue 6 was found to be 66-fold ERalpha-selective and demonstrated uterine estradiol antagonism.