Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion.
To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112 +/- 0.020 min-1 vs 0.065 +/- 0.015 min-1 at rest) (P < 0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080 +/- 0.018 min-1 vs 0.034 +/- 0.013 min-1 at rest) (P < 0.001), with an excellent correlation with the LV Kmono (r = 0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158% +/- 81%) than that in LV Kmono (79% +/- 39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects.


Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.
The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P < 0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/ALC and CHIT groups (P<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve.


Physiotherapy in an advanced rehabilitation pathway for patients after hip and knee arthroplasty: A proposal.
Accelerated rehabilitation pathway (ARP) decrease patients' hospital length of stay (LOS). A lack of evidence exists on physiotherapy management and outcome as part of ARP in South Africa (SA). Our study will aim to determine whether early mobilisation and increased frequency of physiotherapy treatments for participants after hip or knee arthroplasty surgery on post-operative day 0 (POD 0) affect outcome. A quantitative prospective cohort study incorporating ARP on (n = 60) non-randomised elective hip and knee arthroplasty participants will be compared with a more conservatively managed historical control group (n = 60). The physiotherapy protocol includes early mobilisation and exercises 1-3 h post-operatively on POD 0 and a second mobilisation and exercise session, 1-2 h later. Outcomes measures are as follows: hours for LOS, the WOMAC measured pre-operatively, 6 weeks and 3 months post-operatively, 30-day readmission for safety and cost comparison between the prospective and historical cohorts. Descriptive statistics will be undertaken. A paired t-test will be used to analyse each of the outcome measures across the time periods if data are normally distributed. Length of stay, WOMAC score and cost data will be compared between the groups, using a Mann-Whitney U test. The occurrence of adverse events will be compared between the groups using Pearson's chi-square tests. The confidence interval will be set at 95% and p = 0.05 will be considered statistically significant. Globally, ARP's are successfully implemented to manage patients presenting with hip and knee osteoarthritis (OA). Research investigating physiotherapy protocols in an ARP is lacking in the literature. Achieving the same-day discharge after hip and knee arthroplasty surgeries may help elective surgery backlogs and waiting lists in a more cost-effective manner. The same day discharge after arthroplasty may be a cost-effective management option in the future. Pan African Clinical Trial Registry, PACTR202103637993156.


The cooperative effect of the satin and beige mutations in the suppression of NK and CTL activities in mice.
The functional activity of natural killer (NK) cells has been found to be modulated by several point mutations associated with coat color. The most commonly studied gene, beige (Bg), has been found to block a postrecognition event in the lytic cycle. Four other coat color mutations in the mouse (satin, leaden, fuzzy, pale ears) were studied for their effect on NK cell function, and only one, satin (Sa), was found to be suppressive. When both the Sa and Bg mutations were present in the same animal, their effects were synergistic in the suppression of NK levels. Normal numbers of NK cells were present in these double mutants, as determined by the frequency of IgG2b binding cells and by antiasialo GM1 staining. The ability of Sa/Bg NK cells to recognize and bind targets suggests that the defect is localized in the postbinding cytolytic pathway. These genes were not specific for NK cells and also suppressed alloimmune cytolytic T lymphocyte function. Since Sa/Bg mice are much more suppressed in NK function than Bg mice, we suggest that this double mutant may be a better model for NK deficiency in vivo.


Increased Body Mass Index Is a Risk Factor for Poor Clinical Outcomes after Radical Prostatectomy in Men with International Society of Urological Pathology Grade Group 1 Prostate Cancer Diagnosed with Systematic Biopsies.
The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422-0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598-0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660-0.777). Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.


Role of addition of dexamethasone to lignocaine 2% with adrenaline in dental nerve blocks for third molar surgery: A prospective randomized control trial.
Dexamethasone has been frequently used in oral surgical procedure and accepted by oral and maxillofacial surgeon community worldwide. However, this is the first clinical trial that used dexamethasone as adjuvant with lignocaine in dental nerve block (DNB). The purpose of this double-blind, randomized control trial (RCT) was to compare the effect of dexamethasone with normal saline (NS) in a lignocaine DNB. This prospective, double-blind, RCT was carried out after obtaining approval from the Institutional Ethical Committee. In forty patients, the present placebo-controlled clinical trial was conducted; allocated randomly into two groups: study group (SG) or control group (CG). The single-dose submucosal dexamethasone or NS injection was administered immediately after 2% lignocaine with epinephrine 1:2,00,000 nerves block during mandibular third molar surgery (TMS). Visual analog scale score, number, and exact time nonsteroidal anti-inflammatory drugs were administered were used to measure postoperative analgesia in 2nd and 7th days. All the data were entered into the Spreadsheet (Excel, Microsoft) and Chi-square test, Mann-Whitney U-test, Student's paired and unpaired t-test, and Fisher exact test were used. This study found maximum duration of DNB in SG was 248.88 min and in CG was 175.44 min, whereas minimum duration in SG was 197 min and in CG was 140.78 min. Dexamethasone prolongs the action of lignocaine 2% in DNB for TMS.


Clinical and pathological characterization of 158 consecutive and unselected oligometastatic breast cancers in a single institution.
Data about incidence, biological, and clinical characteristics of oligometastatic breast cancer (OMBC) are scarce. However, these data are essential in determining optimal treatment strategy. Gaining knowledge of these elements means observing and describing large, recent, and consecutive series of OMBC in their natural history. We collected data retrospectively at our institution from 998 consecutive patients diagnosed and treated with synchronous or metachronous metastatic breast cancer (MBC) between January 2014 and December 2018. The only criterion used to define OMBC was the presence of one to five metastases at diagnosis. Of 998 MBC, 15.8% were classified OMBC. Among these, 88% had one to three metastases, and 86.7% had only one organ involved. Bone metastases were present in 52.5% of cases, 20.9% had progression to lymph nodes, 14.6% to the liver, 13.3% to the brain, 8.2% to the lungs, and 3.8% had other metastases. 55.7% had HR+/HER2- OMBC, 25.3% had HER2+OMBC, and 19% had HR-/HER2- OMBC. The HR+/HER2- subtype statistically correlated with bone metastases (p = 0.001), the HER2+subtype with brain lesions (p = 0.001), and the HR-/HER2- subtype with lymph node metastases (p = 0.008). Visceral metastases were not statistically associated with any OMBC subtypes (p = 0.186). OMBC-SBR grade III was proportionally higher than in the ESME series of 22,109 MBC (49.4% vs. 35.1%, p < 0.001). OMBC is a heterogeneous entity whose incidence is higher than has commonly been published. Not an indolent disease, each subgroup, with its biological and anatomical characteristics, merits specific management.


The effect of virtual interviews on the musculoskeletal radiology fellowship match.
Resulting from the COVID-19 pandemic, a virtual interview format was adopted in lieu of in-person interviews for fellowship recruitment. The purpose of this study is to analyze the potential effect that virtual interviews have on musculoskeletal radiology fellowship match results and collect opinions of the process. An anonymous survey was sent to 87 listed US-based musculoskeletal radiology fellowship directors, who were asked for their 2019-2020 and 2020-2021 match data: fellowship positions, interviewees, ranked interviewees, and matched ranks. They rated effectiveness of virtual interviews on a ten-point scale (1 poor-10 excellent) and provided an ideal percentage of future interviews to be conducted virtually. Thirty responses were received (34.4% response rate). Primary analysis found significant increase in the mean number of candidates ranked in 2020-2021, 14.6 to 17.5 (p = 0.047). The mean rank of matched applicants increased from 6.02 to 6.43, without significance (p = 0.821). Secondary analysis, which attempted to exclude internally matched programs, found significant increases in 2020-2021 in the mean number of applicants-28.7 to 32.4 (p = 0.017), interviews conducted-17.8 to 21.3 (p = 0.007), and candidates ranked by programs-16.3 to 19.8 (p = 0.015). The mean rank of matched applicants increased from 6.39 to 7.03, without significance (p = 0.713). With results showing an increase in applications, interviews conducted, and ranked applicants while lowering the average rank of matched candidates, musculoskeletal radiology fellowship directors should consider interviewing more applicants than they usually would in the prior in-person recruitment format.


Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.
To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients. The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA. Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05). OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.


Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.
Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. EU's Seventh Framework Programme. For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.


Daily cycle of fos expression within hypothalamic POMC neurons of the male rat.
The activity of hypothalamic pro-opiomelanocortin (POMC) neurons is known to display a circadian cycle. We hypothesized that the existence of a c-Fos responsive element (AP-1 site) within the POMC gene sequence might reflect the ability of POMC neurons to express c-fos proto-oncogene during circadian increase of their neuronal activity. To this aim, adult male rats previously kept under a controlled 12 h light/12 h dark schedule were sacrificed every 4 h throughout the 24 h cycle and their brains processed for Fos and/or POMC immunocytochemistry. Here we show that, specifically during the dark period of the cycle, the mediobasal hypothalamic area spontaneously exhibits a strong Fos immunoreactivity, whereas very low Fos labelling was detected during the light period. As postulated, the simultaneous visualisation of both Fos and POMC antigens allowed us to show that this nocturnal induction of Fos occurs almost exclusively at the nuclear level of POMC-producing neurons. These results not only highlight the mechanisms underlying the physiological functioning of the hypothalamic POMC system, but also demonstrate the feasibility of using c-fos expression as a useful tool to assess the pharmacological effect of drugs on the activity of POMC neurons as is the case for many other neuronal systems. Such drugs might be relevant in the treatment of psychosis since an alteration of POMC-related peptide transmission has been reported in the brains of both schizophrenic and depressive patients.


Frequent polymorphic changes but not mutations of TRAIL receptors DR4 and DR5 in mantle cell lymphoma and other B-cell lymphoid neoplasms.
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors DR4 and DR5 have been mapped to chromosome 8p21-22, a region frequently deleted in different lymphoid neoplasms. To investigate the potential alterations of these genes in lymphoid neoplasms, we examined the presence of gene mutations in exons 3, 4, and 9 in 69 cases with mantle cell lymphoma (MCL), 16 with chronic lymphocytic leukemia (CLL), 12 with follicular lymphomas (FL) and 17 with large B-cell-lymphomas (DLBCL), as well as in 4 lymphoid cell lines carrying the t(11;14) translocation, and 91 healthy blood donors. Three CLL and three MCL cases had 8p deletions. Two nucleotide changes in or near the intron 3 splice consensus sequence and a silent change were found. These rare changes were also present in the germ-line of the patients. The DR4 death domain A1322G polymorphism was significantly more frequent in MCL [odds ratio (OR) = 5.9; 95% confidence interval (CI), 1.92-18.1] and CLL (OR = 4.5; CI, 1.18-17) patients than in a sex and age-adjusted healthy population. In contrast, the DR4 exon 4 C626G polymorphism was associated with a significant overall decreased risk for MCL (OR = 0.3; CI, 0.12-0.8). No mutations or cancer-associated polymorphic changes were found in DR5 domains. These findings indicate that mutations of DR4 and DR5 are uncommon in lymphoid neoplasms but DR4 polymorphic alleles may contribute to the pathogenesis of these malignancies.


Pacing Over the Guidewire in Cardiac Structural Intervention: A Practical Guide.
Left ventricular access for aortic valve intervention provides the opportunity to deliver rapid pacing over the guidewire for device positioning and deployment. Temporary pacing delivered via the left ventricle can obviate the need for venous access and has been shown to be a safe alternative to temporary right ventricular pacing. The technique requires some basic knowledge and experience in temporary cardiac pacing. We outline safe practical steps and common pitfalls in using this technique.


Differences in interactional behaviour in postpartum depression with and without pre-existing mental disorder.
Mothers with postpartum depression (PPD) show impaired affects and behaviour patterns in the mother-child interaction, which affects an infant's emotional and cognitive development and the maternal course of disease. However, impairment of the mother-child relationship does not occur in every case of PPD. The aim of this exploratory-descriptive video-based study was to investigate the possible associations between mother-child interactions and aspects of maternal biography and clinical history, with a focus on pre-existing mental disorder. Sixty-two mother-child dyads (31 mothers with PPD and pre-existing mental disorders and 31 mothers with PPD but no further mental disorder) hospitalized at the mother and baby unit (MBU) of the LWL-Hospital Herten were included in this study. The Marcé Clinical Checklist and the "Mannheimer Beurteilungsskala zur Erfassung der Mutter-Kind-Interaktion im Säuglingsalter" (MBS-MKI-S) were used to explore sociodemographic and clinical parameters, and video-based interaction behaviour was examined. Mother-infant interaction behaviour showed a significant group difference on the MBS-MKI-S-Vm subscale (variability in maternal behaviour) before psychiatric treatment (exact Mann-Whitney U test: U = 555, p = 0.023), with higher scores in mothers with a pre-existing mental disorder. Furthermore, significant differences were shown on the MBS-MKI-S-RSm (maternal reactivity/sensitivity) (U = 259, p = 0.019) and MBS-MKI-S-Rc (child's reactivity) subscales at discharge (U = 251, p = 0.021). Among mothers with a pre-existing diagnosis, the MBS-MKI-S-Tm (maternal tenderness) and MBS-MKI-S-Rc (child's reactivity) subscales were significantly correlated after treatment. Mothers with PPD and a pre-existing mental disorder displayed significantly more behavioural variability than mothers with only PPD. Maternal behaviour seems to influence the child's responsive behaviour; thus, mothers and their children can benefit from inpatient treatment at an MBU. Further investigations with larger samples should be conducted.


Examination of normalized pulse volume-blood volume relationship: toward a more valid estimation of the finger sympathetic tone.
The pulsatile ac component (DeltaI) superimposed on the transmitted dc components (I: tissue plus blood) are obtained from a near-infrared finger photoplethysmogram using a wavelength of 810 nm. Only the dc component is given in an ischaemic circulatory state (I(t): tissue only). Based on Lambert-Beer's law, normalized pulse volume (NPV; =DeltaI/I) and blood volume [BV; =ln(I(t)/I)] have recently been advocated as quantitative measures. In this study, the NPV-BV relationship was examined using the finger occlusion method during rest and mental arithmetic in 16 female undergraduates. Finger vascular tone during stress was evaluated by the distance of the linear and parallel NPV-BV regression lines (D(NB)) between rest and stress conditions. A reference standard was provided by the linear regression lines of compliance index (CI=NPV/pulse pressure) and BV to the transmural pressure. The estimates at 40 mmHg of transmural pressure, as an arbitrarily chosen reference point, were calculated (CI40 and BV40). D(NB) correlated well with them (r=0.81 and 0.94, respectively). The multiple regression with mean blood pressure indicated that the combination of D(NB) and the reactivities in heart period could explain approximately 50% of valiance in pressor response. In conclusion, D(NB) is easily obtainable from the NPV-BV function and seems to be more specific and valid than NPV as an index of finger sympathetic tone, since it adjusts the mechanical effect of arterial distending pressure.


Pioglitazone stabilizes atherosclerotic plaque by regulating the Th17/Treg balance in AMPK-dependent mechanisms.
Pioglitazone (PIO), a thiazolidinediones drug, is a well-known anti-diabetic medicine, but its anti-atherosclerotic effects remain controversial. Thus it is important to investigate the effects of PIO on atherogenesis and the relevant mechanisms. For in vitro studies, primary cultured or AMP-activated protein kinase (AMPK) inhibited splenocytes were treated with oxidized low density lipoprotein (ox-LDL) or ox-LDL plus PIO. Percentage of T helper 17 (Th17) and regulatory T (Treg) cells were determined by flow cytometry. Expression of AMPK, interleukin-17 (IL-17) and forkhead box P3 (FoxP3) were detected by Western blots. For in vivo studies, apolipoprotein E-deficient (apoE-/-) mice fed with western diet were treated with PIO or vehicle for 8 weeks respectively. Percentage of Th17 and Treg cells in spleen were measured by immunohistochemical analysis. The atherosclerotic lesions were analyzed using oil red O staining, and collagen types I and III in atherosclerotic lesions were stained by Sirius red. Expression of IL-17 and FoxP3 were determined by quantitative polymerase chain reaction. In cultured primary splenocytes, PIO dramatically inhibited Th17 and raised Treg. Intriguingly, pharmacological and genetic AMPK inhibitions abolished PIO-induced Treg elevation and Th17 inhibition. Moreover, PIO significantly induced AMPK phosphorylation, decreased IL-17+ and increased FoxP3+ cells in spleen of apoE-/- mice. Finally, PIO did not alter plaque area, but intriguingly, stabilized atherosclerotic plaque through collagen induction in apoE-/- mice. PIO treatment also improved Th17/Treg balance in atherosclerotic lesions. PIO exhibits anti-atherosclerotic effects for stabilization of atherosclerotic plaque through regulating the Th17/Treg balance in an AMPK-dependent manner.


Purification of landfill gas by extracted calcium ions from municipal solid waste incineration fly ash.
This study proposes the utilization of CO2 based on the purification of landfill gas (LFG). The process included absorption of CO2 from LFG using monoethanolamine (MEA) absorbent, extraction of calcium ions from municipal solid waste incineration (MSWI) fly ash using various acids, and formation of calcium carbonate using the extracted calcium ions. During LFG purification, the concentration of CH4 in the gas after absorption was time dependent. The pH swing method was used for the extraction of calcium ions and comprised three phases: calcium ion leaching from MSWI fly ash phase, removal of cations from the supernatant, and calcium ion recovery. Hydrochloric and nitric acids, known as strong acids, and citric, acetic, and formic acids, which are weak acids, were used as extraction agents. Hydrochloric acid, nitric acid, acetic acid, and formic acid showed significant calcium ion recovery rates of 99.32%, 99.18%, 98.35%, and 97.99%, respectively, whereas citric acid showed a relatively low recovery rate of 82.82%. The extracted calcium ions were converted into calcium carbonate by reacting with ionic CO2 in the saturated MEA. The calcium carbonate formed showed different crystal structures based on the extraction agent used: aragonite for hydrochloric acid and nitric acid, amorphous CaCO3 for citric acid, vaterite for acetic acid, and calcite for formic acid. The results of this study can be applied to various CO2 utilization processes based on LFG and MSWI fly ash.


Effects of comprehensive nursing on postoperative complications, mental status and quality of life in patients with glioma.
The complexity and refractory of brain glioma requires treatment that should involve a multidisciplinary approach to improve quality of care and fulfill patients' needs. To explore the effects of comprehensive nursing on postoperative complications, psychological state and quality of life in patients with brain glioma. A total of 106 patients with confirmed brain gliomas admitted to Nanchong Central Hospital between January 2019 and May 2021 were selected by random sampling. They were categorized into an observation group and a control group using a random number table with 53 patients in each group. Patients in the observation group were given comprehensive nursing in addition to conventional nursing and patients in the control group were given conventional nursing. The overall incidence of postoperative complications including limb dysfunction, high fever and epilepsy was compared between the two groups. The mental status was evaluated in the two groups before and after intervention using self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Quality of life was assessed and compared using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire between the two groups before and after the intervention. After intervention, the overall incidence of postoperative complications was significantly lower in the observation group (7.55%) than that in the control group (20.75%) (P < 0.05). Before intervention, there was no significant difference in SAS and SDS scores between the two groups (P > 0.05). However, after intervention, scores of SAS and SDS decreased in the two groups compared with those before intervention, and the scores of SAS and SDS were lower in the observation group than in the control group (all P < 0.05). There was no significant difference in quality of life between the two groups before the intervention (P > 0.05). In contrast, quality of life increased in the two groups compared with those before intervention, and it was higher in the observation group than in the control group (P < 0.05). Comprehensive nursing can reduce the incidence of postoperative complications, improve the psychological state of anxiety and depression and improve quality of life in patients with brain glioma.


The sensitivity of field isolates of Eimeria acervulina type to monensin.
The sensitivity of 32 field isolates of Eimeria acervulina to 100 ppm monensin was investigated in birds inoculated with 10(6) or 10(3) oocysts. Isolates were obtained from broiler farms where monensin had been used (broiler isolates) and from breeder farms where the drug had never been employed (breeder isolates). The drug was not completely effective against breeder isolates. When broiler and breeder isolates were compared, monensin was less effective against the former irrespective of whether weight gain or oocyst production was used to measure the infection. It is likely therefore that resistance to monensin may have been acquired as a result of its use in broiler chickens. The drug had activity against broiler isolates, however with more prolonged use, fully resistant strains may eventually emerge.


Polymorphonuclear leukocytes produce thromboxane A2-like activity during phagocytosis.
Homogenates of phagocytosing polymorphonuclear leukocytes obtained from rabbit peritoneum were incubated with the prostaglandin endoperoxides PGG2 or PGH2. After 2 min at 0degree C, incubation mixtures contained an increased rabbit aorta contracting activity. Ether extracts of incubation mixtures contained a substance which contracted the superfused strips of rabbit aorta and coeliac artery and had a half life which was similar to thromboxane A2. The generation of thromboxane A2-like activity from PG endoperoxides was prevented by boiling the homogenate prior to incubation, or by pretreatment with benzydamine, a drug which blocks thromboxane formation in platelets. Production of thromboxane A2-like material by leukocyte homogenates was compared with platelet microsomal thromboxane synthetase.


Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials.
Randomized trials of therapies that primarily lowered triglycerides have not consistently shown reductions in cardiovascular events. We performed a systematic review and trial-level meta-regression analysis of 3 classes of lipid-lowering therapies that reduce triglycerides to a greater extent than they do low-density lipoprotein cholesterol (LDL-C): fibrates, niacin, and marine-derived omega-3 fatty acids. Key inclusion criteria were a randomized controlled trial that reported major vascular events. We also incorporated data from a previous meta-regression of 25 statin trials. The main outcome measure was the risk ratio (RR) for major vascular events associated with absolute reductions in lipid parameters. A total of 197 270 participants from 24 trials of nonstatin therapy with 25 218 major vascular events and 177 088 participants from 25 trials of statin therapy with 20 962 major vascular events were included, for a total of 374 358 patients and 46 180 major cardiovascular events. Starting with non-high-density lipoprotein cholesterol, a surrogate for very-low-density lipoproteins and low-density lipoproteins, the RR per 1-mmol/L reduction in non-high-density lipoprotein cholesterol was 0.79 (95% CI, 0.76-0.82; P<0.0001; 0.78 per 40 mg/dL). In a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for low-density lipoproteins and very-low-density lipoproteins, respectively), the RR was 0.80 (95% CI, 0.76-0.85; P<0.0001) per 1-mmol/L (0.79 per 40 mg/dL) reduction in LDL-C and 0.84 (95% CI, 0.75-0.94; P=0.0026) per 1-mmol/L (0.92 per 40 mg/dL) reduction in triglycerides. REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) was a significant outlier and strongly influential trial in the meta-regression. When removed, the RRs became 0.79 (95% CI, 0.76-0.83; P<0.0001) per 1-mmol/L (0.78 per 40 mg/dL) reduction in LDL-C and 0.91 (95% CI, 0.81-1.006; P=0.06) per 1-mmol/L (0.96 per 40 mg/dL) reduction in triglycerides. In regard to omega-3 dose, each 1 g/d eicosapentaenoic acid administered was associated with a 7% relative risk reduction in major vascular events (RR, 0.93 [95% CI, 0.91-0.95]; P<0.0001), whereas there was no significant association between the dose of docosahexaenoic acid and the relative risk reduction in major vascular events (RR 0.96 [95% CI, 0.89-1.03]). In randomized controlled trials, triglyceride lowering is associated with a lower risk of major vascular events, even after adjustment for LDL-C lowering, although the effect is less than that for LDL-C and attenuated when REDUCE-IT is excluded. Furthermore, the benefits of marine-derived omega-3 fatty acids, particularly high-dose eicosapentaenoic acid, appear to exceed their lipid-lowering effects.


Individual dose recommendations for drug interaction between tacrolimus and voriconazole in adult liver transplant recipients: A semiphysiologically based population pharmacokinetic modeling approach.
The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole.


Editorial: The latest in imaging technology.
"Seeing is believing" - this issue of Biotechnology Journal features a collection of articles on the latest in imaging technologies.


A large volume of visceral adipose tissue leads to severe acute pancreatitis.
Obesity plays an important role in acute pancreatitis. Assuming that the volume of visceral adipose tissue (VAT) directly influences the severity of acute pancreatitis, we investigated the relationship between VAT and acute pancreatitis. Data were collected consecutively from 124 patients who were diagnosed with acute pancreatitis. Body mass index (BMI) was calculated from the database. Computed tomography was performed in all patients, and VAT, subcutaneous adipose tissue (SAT), and waist circumference (WC) were measured at the level of the intervertebral disk between L2 and L3. Atlanta criteria were adopted to define severe acute pancreatitis. Clinical courses were investigated, and the Ranson and acute physiology and chronic health evaluation II (APACHE II) scores were calculated for all patients. Forty-eight patients had severe acute pancreatitis (38.7%), and 76 were mild cases. BMI, VAT, SAT, and WC were correlated with the severity of acute pancreatitis in a univariate analysis, but only VAT had a strong correlation with severe acute pancreatitis in the multivariate analysis. In a trend analysis, not only severity but also the presence of pseudocysts (local complication) and prognostic factors (Ranson and APACHE II scores) were significantly related to VAT volume. In particular, the presence of a pancreatic pseudocyst was strongly related to VAT volume (p < 0.001). In acute pancreatitis, peripancreatic VAT has a stronger correlation with severe acute pancreatitis than BMI or WC. VAT volume is strongly correlated with the formation of a pseudocyst and with systemic inflammatory response syndrome in patients with acute pancreatitis and high VAT volume may lead to severe acute pancreatitis.


Quantitative Aspects of Gas-Phase Metal Ion Chemistry: Conservation of Spin, Participation of f Orbitals, and C-H Activation and C-C Coupling.
In this Featured Article, I reflect on over 40 years of guided ion beam tandem mass spectrometry (GIBMS) studies involving atomic metal cations and their clusters throughout the periodic table. Studies that have considered the role of spin conservation (or lack thereof) are a primary focus with a quantitative assessment of the effects examined. A need for state-specific studies of heavier elements is noted, as is a more quantitative assessment of spin-orbit interactions in reactivity. Because GIBMS experiments explicitly evaluate the kinetic energy dependence of reactions over a wide range, several interesting and unusual observations are highlighted. More detailed studies of such unusual reaction events would be welcome. Activation of C-H bonds and ensuing C-C coupling events are reviewed, with future work encouraged. Finally, studies of lanthanides and actinides are examined with an eye on understanding the role of f orbitals in the chemistry, both as participants (or not) in the bonding and as sources/sinks of electron density. This area seems to be ripe for more quantitative experiments.


Retinal and optic nerve diseases.
Basic knowledge of the normal appearance and variations of the equine fundus coupled with frequent practice in ophthalmology will allow equine practitioners to be confident when assessing the equine fundus during ophthalmic examinations. Once the normal variations are mastered, appreciation of retinal, choroidal, optic nerve, and vitreal abnormalities is possible. Congenital and acquired lesions of the equine retina, optic nerve, and vitreous are discussed and illustrated.


A cytogenetic study of subcutaneous murine macrophages and multinucleate giant cells.
Macrophages and multinucleate giant cells (MGC), collected by subcutaneous implantation of melinex discs into the dorsum of mice for 7 days, were examined cytogenetically. Two per cent of the metaphases seen were polyploid and were considered to represent dividing MGC. Twenty-two per cent of the diploid metaphases showed chromosomal damage. Seventy per cent of damage consisted of chromosomal gaps, but the remaining 30% consisted of breaks and chromosomal fragments which would lead to unbalanced karyotypes in the next generation. More than 50% of the polyploid metaphases analysed had chromosomal damage, including 16.6% which displayed premature chromatin condensation, the damage being more severe in polyploid than in diploid metaphases. The chromosomal damage parallels that previously reported in resident peritoneal macrophages and in cultured exudate macrophages. The cause of such damage is unclear, but it was concluded that, because of the extent of damage, mitosis is unlikely to play a major part in the maintenance of macrophages or MGC at inflammatory sites.


HLA class II antigens and T lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon.
Nasal polyps are characterized by a proliferation of the epithelial layer of the mucosa, cellular infiltrates and other pathological changes; however the mechanisms involved in polyp pathogenesis remain largely unclear. We have taken two different approaches to study the cellular events involved in nasal polyposis. First, through use of immunohistochemical methods, we have studied the expression of HLA class II antigens in epithelial cells of nasal polyps and the distribution of lymphocytes in the epithelium and in the subepithelial layer in patients with clinical conditions, such as asthma, atopy, aspirin intolerance or cystic fibrosis, and in subjects with an absence of concomitant diseases. Second, in order to investigate whether HLA class II expression is controlled at the pre- or post-transcriptional level, we studied the effect of interferon gamma (INF gamma) on epithelial cells in primary culture, which were derived from HLA class II negative and HLA class II positive nasal polyps. Total RNA was extracted from the cells and reverse-transcribed, and the c-DNA corresponding to DR, DP, DQ loci was amplified by PCR. Expression of HLA class II antigens by the epithelia of nasal polyps was more common in the presence rather than in the absence of concomitant asthma, atopy or cystic fibrosis (59% versus 40%). HLA-DR was the only HLA class II antigen expressed in the seven polyps taken from cystic fibrosis patients. The number of CD8+ cells was significantly higher in polyps associated with known clinical conditions and HLA class II antigen expression than it was in 'isolated' polyps and in HLA class II negative polyps. RNA transcripts for at least one or all three HLA-DR, DP and DQ antigens were detected in 10 cultures of the II HLA class II positive polyps. Conversely, 8 of 10 cultures derived from HLA class II negative polyps did not express HLA class II transcripts in the absence of INF gamma. Adding INF gamma (100 U/ml) to the latter cell cultures caused expression of transcripts of one or more HLA class II genes. We have shown that HLA class II antigens were more frequently detected in polyps of patients with an identified clinical syndrome than in those of asymptomatic subjects. Our results also suggest that IFN gamma regulates expression of HLA class II antigens in airway epithelial cells of the nasal polyps at the transcriptional level, and that cultured cells from nasal polyps represent a suitable model to investigate immune mechanisms involved in diseases such as atopy, asthma and cystic fibrosis.


Genetic and dental study of patients with celiac disease.
The aim of this work was to study the pattern of inheritance of celiac disease in a group of Saudi patients and to compare oral mucosal and dental clinical findings in these patients to those of healthy controls. Fifty patients suffering from celiac disease were screened for dental evaluation. They were subjected to clinical genetic examination, pedigree construction, oral mucosal and dental clinical evaluation. An autosomal recessive mode of inheritance was evident in some of the studied cases, while others showed sporadic occurrence. Oral mucosal and dental clinical examinations revealed recurrent oral ulcerations, enamel hypoplasia in most of the celiac disease patients. Pedigree analysis of families is important to identify the mode of inheritance. Oral mucosal and dental clinical examinations are important in diagnosing and monitoring cases of celiac disease.


Recent advances in our understanding of giant cell arteritis pathogenesis.
Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4+ T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8+ T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling.


Sarcoma Pulmonary Metastatic Disease: Still a Chance for Cure.
Tumors of soft tissue origin are not common but are increasing in incidence. Given the rare and heterogeneous nature of the disease, deciding on an effective treatment approach to the patient can be challenging. Approximately 20-50% of patients with sarcoma will develop metastases to the lung via hematogenous spread. Despite improvements in systemic therapy options for patients with metastatic disease to the lung, surgical resection of metastases is often the preferred option in patients who are safe surgical candidates. Clearance of metastatic disease with surgical resection has been proven to be cost-effective and can improve chances for long term survival. Deciding on who may benefit from surgical resection is best achieved in a multidisciplinary setting.


Intuition, reason, and metacognition.
Dual Process Theories (DPT) of reasoning posit that judgments are mediated by both fast, automatic processes and more deliberate, analytic ones. A critical, but unanswered question concerns the issue of monitoring and control: When do reasoners rely on the first, intuitive output and when do they engage more effortful thinking? We hypothesised that initial, intuitive answers are accompanied by a metacognitive experience, called the Feeling of Rightness (FOR), which can signal when additional analysis is needed. In separate experiments, reasoners completed one of four tasks: conditional reasoning (N=60), a three-term variant of conditional reasoning (N=48), problems used to measure base rate neglect (N=128), or a syllogistic reasoning task (N=64). For each task, participants were instructed to provide an initial, intuitive response to the problem along with an assessment of the rightness of that answer (FOR). They were then allowed as much time as needed to reconsider their initial answer and provide a final answer. In each experiment, we observed a robust relationship between the FOR and two measures of analytic thinking: low FOR was associated with longer rethinking times and an increased probability of answer change. In turn, FOR judgments were consistently predicted by the fluency with which the initial answer was produced, providing a link to the wider literature on metamemory. These data support a model in which a metacognitive judgment about a first, initial model determines the extent of analytic engagement.


Dietary and microbiome evidence in multiple myeloma and other plasma cell disorders.
Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes mellitus, diet, and the human intestinal microbiome have been linked to the pathogenesis of MM. In this article, we provide a detailed review of dietary and microbiome factors involved in the pathogenesis of MM and their impact on outcomes. Concurrent with treatment advancements that have improved survival in MM, focused efforts are needed to reduce the burden of MM as well as improve MM specific and overall outcomes once MM is diagnosed. The findings presented in this review will provide a comprehensive guide on the evidence available to date of the impact of dietary and other lifestyle interventions on the gut microbiome and on MM incidence, outcomes, and quality of life. Data generated from such studies can help formulate evidence-based guidelines for healthcare providers to counsel individuals at risk such as those with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) as well as MM survivors with respect to their dietary habits.


Genetic basis and carrier detection of hemophilia B of Chinese origin.
We have characterized the genetic defects of 17 hemophilia B patients of Chinese origin by means of the polymerase chain reaction (PCR) and direct sequencing. The single-strand conformation polymorphism (SSCP) was used as an initial screening method to analyze the entire coding region and the flanking introns of each individual's factor IX gene. The abnormal exons were subsequently amplified and the nucleotide sequence determined. Of the 17 patients studied, 16 had single point mutations and one had a gross gene deletion of exons VII and VIII of factor IX. Among these 16 factor IX variants with point mutations 13 were missense and two were nonsense mutations. The remaining one had a nucleotide deleted, resulting in frame shifting at amino acid residue 97. A total of ten novel mutations, including the one with gross gene deletion, are reported in this study which have not been described previously. Five of the remaining seven variants were missense mutations with novel amino acids substituted for residues 127, 132, 180, 207, and 215, respectively. Mutations containing different amino acid residues at those positions have been reported. The last two are variants that have already been described to contain mutations at amino acid residues 333 and 365, respectively. To evaluate the efficiency of SSCP analysis in assessing the mutated exons and to further confirm our results we sequenced the entire exons of all 17 factor IX genes. The mutations detected by SSCP method were indeed the only mutation identified in each factor IX variant.(ABSTRACT TRUNCATED AT 250 WORDS)


Carcinogenesis and cyclooxygenase: the potential role of COX-2 inhibition in upper aerodigestive tract cancer.
Cyclooxygenase-2 (COX-2) is upregulated in a number of epithelial cancers, including in upper aerodigestive tract (UADT) premalignant and malignant lesions. The purpose of this review is to provide a comprehensive examination of the potential of COX-2 inhibition in prevention of UADT premalignant and malignant disease. A Medline and Cancerlit literature search was conducted for the period 1993-2002, and identified literature was reviewed. There is evidence from in vitro studies, as well as animal models, that inhibition of COX-2 may suppress carcinogenesis by affecting a number of pathways of carcinogenesis, promoting apoptosis and inhibiting angiogenesis. Preliminary studies of gastro-intestinal (GI) carcinogenesis suggest that COX-2 inhibitors may represent an approach to the chemoprevention of epithelial cancers. COX-2 inhibitors may have a potential role in chemoprevention of UADT cancer, and clinical trials appear warranted.


Intraoperative removal of pancreatic duct calculus with a rigid ureterorenoscope and ultrasonic lithotripsy.
A 51-year-old man with chronic relapsing pancreatitis and recurrent episodes of acute attacks had an impacted ductal stone deep in the head of the pancreas. A staghorn calculus, 1 cm in diameter, was successfully disintegrated and removed intraoperatively with use of a visual endourologic technique and ultrasonic lithotripsy. Because of a dilated pancreatic duct and pseudocyst formation near the tail of the pancreas, distal pancreatic resection and longitudinal pancreaticojejunostomy were performed. Postoperatively, no pancreas irritation has been verified, and the patient has remained without symptoms.


Antifungal agents used for deep-seated mycotic infections.
The main antifungal agents used for deep-seated mycotic infections are the broad-spectrum antifungal drug amphotericin B, the narrow-spectrum agent flucytosine, and the newer broad-spectrum agents miconazole and ketoconazole. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. 2-Hydroxystilbamidine is used only in indolent cases of blastomycosis; however, this condition is usually treated with amphotericin B. Clinical experience with the newer agents is limited. Not all patients from whom fungal agents have been isolated require treatment; the extent of the fungal infection should be determined, when possible, for evaluation of the need for treatment.


Back diffusion of chlorinated solvent contaminants from a natural aquitard to a remediated aquifer under well-controlled field conditions: predictions and measurements.
Vertical profiles of tetrachloroethene (or perchloroethylene, PCE) and trichloroethene (TCE) were used to validate a diffusion process in a natural aquitard at Dover Air Force Base, Delaware. PCE and TCE distributions in the aquitard underlying an unconfined aquifer were sampled from core tubes obtained at four times over the course of a 35-month field investigation within "test cells" that were isolated from the surrounding ground water by means of grout-sealed steel sheetpile barriers (Mackay et al. 2000). For the final 23 months of this period, boundary conditions at the aquifer/aquitard interface were such that a "back diffusion" of contaminants from the aquitard was induced. Modeling predictions of concentration changes were made on the basis of the earliest coring results and an assumption of sorption-retarded diffusion and using laboratory information about sorption and diffusion characteristics of the media. The predictive modeling was complicated by the fact that "initial" and "final" PCE and TCE distributions in the aquitard were measured at different (albeit proximate) coring locations, such that results reflect spatial variations in aquitard characteristics. This problem was solved by means of an inverse interpretation that involved spatial "translation" of observed profiles on the basis of the laboratory characterizations and assuming a common aquifer-side contaminant history. Predictions indicated substantial change in PCE and TCE concentrations within the upper aquitard (near the aquifer/aquitard interface) and the development of a back-diffusion profile up into the aquifer. Modeling also predicted comparatively minor profile changes in the deeper aquitard, and especially in the deep layer where sorption was strongest. All of these predicted effects were observed in the coring results. Although not exact, the agreement between predictions and observations was sufficiently good to justify the basic tenets of the diffusion model and to support a conclusion that major processes of advection and/or transformation were unimportant within the 35-month time scale of this work.


Family cohesion and attention deficit exert an influence on visits to the dentist in early adolescence.
To determine whether family environment, signs of attention deficit/hyperactivity disorder (ADHD) and oral health literacy (OHL) are associated with visits to the dentist in adolescents. A school-based cross-sectional study was conducted with a representative sample of 448 12-year-old adolescents enrolled at schools in the city of Cajazeiras, Brazil. The adolescents answered a validated questionnaire addressing family cohesion and adaptability (FACES III), an OHL measure (Brazilian Rapid Estimate of Adult Literacy in Dentistry [BREALD-30]) and a questionnaire addressing the history of visits to the dentist and previous toothache experience. The parents answered a questionnaire addressing sociodemographic characteristics. Parents and teachers answered the inattention and hyperactivity/impulsivity subscales of the Swanson, Nolan & Pelham (SNAP-IV) questionnaire for the detection of signs of ADHD. Multiple Poisson regression with robust variance was used for data analysis (α = 5%). The prevalence of having visited a dentist some time in life was higher among adolescents with enmeshed (PR = 1.08; 95% CI: 1.01-1.15) and connected (PR = 1.06; 95% CI: 1.01-1.13) families and those with attention deficit according to parents' reports (PR = 1.09; 95% CI: 1.04-1.14). A family income higher than the Brazilian minimum wage (PR = 1.06; 95% CI: 1.01-1.12) and toothache in the previous six months (PR = 1.05; 95% CI: 1.01-1.11) were also associated with the outcome. Family cohesion and attention deficit according to parental reports influenced visits to the dentist among adolescents. In contrast, OHL was not associated with the outcome.


Histoplasmosis in Veterans Administration hospitals in middle America.
A series of clinical studies of histoplasmosis based on demonstrations of etiology led to descriptions of chronic pulmonary histoplasmosis, the principal type in adults, and amphotericin B as an effective therapy. A participant recreates the atmosphere of discovery during the contributions of a team comprising a mycologist, a surgeon and two physicians using cultures of excised lung and sputum to clearly identify cases of chronic pulmonary histoplasmosis. Subsequently cooperating physicians in several V.A. Hospitals carried out randomized studies of treatment, dosage, and side effects that established Amphotericin B as the sole curative therapy for chronic pulmonary histoplasmosis for 20 years.


Golden Years or Retirement Fears? Private Pension Inequality Among Canada's Immigrants.
Currently, many immigrants are disqualified from Canada's public pension scheme because of residency requirements. In addition, decades of low income and labour market exclusion prohibit many Canadian immigrants from building adequate private pension savings throughout their working life. Together, these factors present serious concerns for immigrant seniors' economic well-being. Using Canadian census data spanning a twenty-year period (1991-2011), we find that income from personal savings plans and investments has declined sharply for both native-born and immigrant Canadians, with recent immigrant cohorts faring worst. However, since 1991, native-born and immigrant men living in Canada for 40-plus years had major gains in private employer pensions (Registered Pension Plans; [RPPs]). Yet RPP income for all other immigrant cohorts remained stable or declined during these decades. Thus, the data demonstrate a worrisome growing private savings gap between native-born men and all others in Canada, with newer immigrants and women faring worst.


Arthrocentesis versus nonsurgical methods in the treatment of temporomandibular disc displacement without reduction.
The aim was to compare the short- and medium-term results of arthrocentesis and conventional treatment (splint, heat, and exercise) in patients with early temporomandibular joint (TMJ) disc displacement without reduction (DDw/oR). One hundred twenty consecutive patients (104 female, 16 male), who had been followed by a multidisciplinary TMJ unit with the diagnosis of DDw/oR were enrolled in this single-blind prospective study. Patients either underwent arthrocentesis or they were given a combination of splint, hot pack, and home exercise program. Visual analog scale (VAS) was used for pain assessment. Maximal mouth opening (MMO), lateral movement, and protrusion were measured. Repeat measurements were performed on the first, third, and sixth months following treatments. Arthrocentesis group consisted of 54 individuals (51 female, 3 male), and the conventional treatment group consisted of 56 individuals (49 female, 7 male). The mean age values of the groups were 33.4 years (range 15-63 years) and 34.8 years (range 17-61 years), respectively. Baseline VAS and MMO values of the arthrocentesis and conventional treatment groups were similar (P > .05). Regarding VAS and MMO, lateral movement, and protrusion, the intragroup analyses showed a statistically significant reduction in both groups compared with baseline values (all P < .01). Regarding VAS values, the difference values between each evaluation and the baseline measurement were significantly higher in the arthrocentesis group, except for the first-month difference. Regarding MMO, lateral movements, and protrusion, the differences between the baseline values and each evaluation thereafter were statistically similar between the 2 groups (P > .05). We conclude that early treatment either with conservative methods or with arthrocentesis is beneficial in DDw/oR. However, arthrocentesis seems to be superior regarding pain management. Therefore, arthrocentesis may be indicated in patients where painful complaints overwhelm despite other conservative treatments.


Prediction of drug distribution into human milk from physicochemical characteristics.
Decisions about the safety of breast feeding during maternal ingestion of drugs require knowledge of the amount of drug which might be present in the milk. For many drugs this has not been studied, and mothers are usually advised against breast feeding. In many cases this is undoubtedly unnecessary, as the total dose to which the baby is exposed is often negligible. It would be very helpful, therefore, to be able to predict the approximate amount of drug which might be present in milk. Existing theory of pH partitioning enables estimation of the distribution of unbound drug, i.e. milk: plasma unbound ratios. However, these ratios are poor estimates of the concentration ratios for whole milk, because whole milk contains proteins and lipid in which drugs will distribute in amounts which depend on their particular physicochemical properties. To predict the milk: plasma concentration ratios for whole milk the amount of drug present in the protein and lipid phases must be considered along with the unbound drug distribution. A 'phase distribution model' has therefore been developed which permits estimation of whole milk: plasma concentration ratios. The model requires a knowledge of the unbound drug concentration ratio, the plasma and milk unbound fractions and the milk lipid: ultrafiltrate partition coefficient. Evaluation of the model by comparison of predicted whole milk ratio values with literature milk: plasma area under the curve (AUC) ratios indicated a trend to overprediction for acidic and neutral drugs and underprediction for basic drugs. Transformation of the phase distribution equation by taking logarithms results in a relationship which can be analysed by multiple linear regression to derive predictive equations for acidic and basic drugs which take into account the relative contributions of each component of the model. Regression of the logarithms of the literature milk: plasma AUC values against the independent variables resulted in good correlations for acidic and basic drugs. The independent variables explained 93.1% and 82.9% of the variance in the values for acidic and basic drugs, respectively, with random scatter of residuals. The equations, together with those to predict unbound fractions of drug in milk and milk lipid: ultrafiltrate partition coefficients, enable the ratio of the milk: plasma AUCs to be estimated for any acidic or basic drug for which the distribution into human milk is not known, using the pKa, octanol: water partition coefficient and plasma protein binding values of the drug. The data set for neutral drugs (n = 3) was too small to develop a correlation equation.(ABSTRACT TRUNCATED AT 400 WORDS)


Three cases of acute distal demyelinating neuropathy with recovery.
Guillain-Barré syndrome (GBS) may present as distal acute inflammatory demyelinating polyradiculoneuropathy (AIDP), with severe distal demyelination of the peripheral nerves in the absence of radiculitis. Clinical course is benign, and prognosis seems favorable, but nerve conduction studies (NCS) findings at nadir may resemble some chronic forms of polyneuropathy, so close follow-up during recovery is needed.


Investigations of vegetable tannins as hair dyes and their interactions with pre-bleached hair fibres.
The aim of this work was to investigate an alternative hair-dyeing method with vegetable colourants as the tannins, as well as the impact of pre-treatment as the bleaching process. Untreated, 1, 2 and 3 times bleached hair tresses that were dyed with tannins in combination with metal salts were characterized. The wash fastness and the colour strength of the vegetable-dyed hair tresses were spectrophotometrically investigated. To determine the colour strength KS and the wash fastness of vegetable-dyed and pre-bleached hair tresses, a three-dimensional colour coordinate system - CIELab - which describes the visual spectra is used. The distance between two colours in the CIELab colour space is expressed by ∆E-values, which are used to identify the wash fastness of the vegetable dye. The hair tresses that had been 3 times pre-bleached showed the highest colour strength and the best wash fastness. The fixation of the tannin-mordant complexes on the hair fibre proceeded effectively just when the hair tresses were bleached before the dying process. It is suggested that the sulphonic acid groups, which increase after bleaching hair, interact with the tannin-mordant hair dye and lead to stronger cross-links between keratinous fibres and tannin-mordant complexes. It was observed that the colour strength of the vegetable-dyed tresses correlates with the bleaching process. The presented results demonstrate that the fixation of the vegetable tannin-mordant dying solution on the hair fibres succeed effectively on pre-bleached hair tresses.


Link between overweight/obese in children and youngsters and occurrence of multiple sclerosis.
The prevalence of overweight/obesity is a major problem in the world, and the number of MS cases is increasing. This literature study examines the relationship between overweight/obesity in children and adolescents and later occurrence of MS. This is a complete literature survey. The search database is primarily Pubmed using MeSH terms "multiple sclerosis", "obesity", and "overweight", and text words not to restrict searches. All included studies show a link between being overweight/obese and the presence of MS among people below 20 years of age. The relation is especially true for young girls. The same relation in boys is not significant. The literature survey convincingly revealed a link between young overweight/obese and occurrence of MS, in particular for girls. There is a need for more and larger studies to investigate the molecular mechanisms that link obesity and MS.


Nerve conduction during acute blood-flow restriction with and without low-intensity exercise Nerve conduction and blood-flow restriction.
Despite being apparently safe for most individuals, the impact of low intensity (LI) blood-flow restricted (BFR) exercise on nerve function and integrity is still obscure. We explored whether BFR (with and without exercise) alters the properties of nerve conduction measured at the level of the restricted limb. Thirteen healthy, young men (22.0 ± 1.7 years) were included in this study. Arterial occlusion pressure was taken at rest. Soleus M- and H-recruitment curves were constructed for all participants. H-wave latencies and amplitudes were obtained in three testing conditions (non-BFR vs. 60 vs. 80% BFR) at four different time points: [#1] non-restricted baseline, [#2] time control either with or without BFR, [#3] non-restricted pre-exercise, [#4] LI exercise either with or without BFR. Nerve conduction was estimated using the difference between the latency of H and M wave. BFR did not affect H-wave amplitude, either with or without exercise. The changes in the difference between H- and M-wave latency of over time were similar between all conditions (condition-by-time interaction: F = 0.7, p = 0.47). In conclusion, our data indicate that performing LI exercise with BFR, set at 60 or 80% BFR, does not exert a negative impact on sciatic-tibial nerve function. Thus, from a neurological standpoint, we provide preliminary evidence that LI BFR exercise may be regarded as a safe mode of resistance training in healthy young men.


Alpha- and beta-subunits of a V-type membrane ATPase in a hyperthermophilic sulfur-dependent archaeum, Thermococcus sp. KI.
The genes encoding alpha- and beta-subunits of a V-type ATPase in a sulfur-dependent hyperthermophilic archaeum, Thermococcus sp. KI, were cloned and sequenced. The deduced amino acid sequences were approximately 60, 50 and 25% identical to those of other archaeal, eukaryotic V-type and E. coli F-type ATPase, respectively. Phylogenetic analysis revealed that Thermococcus ATPase was closely related to that of Thermus, and those of Methanosarcina and Halobacterium.


Pretreatment predictors of posttreatment PSA doubling times for patients undergoing three-dimensional conformal radiotherapy for clinically localized prostate cancer.
To determine whether pretreatment risk groups also predict for posttreatment prostate-specific antigen (PSA) doubling times (PSADTs). Pretreatment risk groups predict for posttreatment biochemical failure (BF) after conformal radiotherapy in patients with prostate cancer and posttreatment PSADTs can predict for prostate cancer-related deaths. The study cohort consisted of 416 patients with clinically localized prostate cancer treated with conformal radiotherapy between 1989 and 2001. The patients were divided into low, intermediate, and high-risk groups. BF was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Patients with BF were grouped according to their PSADT (3 months or less, longer than 3 months to less than 6 months, 6 months to less than 12 months, and 12 months or longer). A Mantle-Haenszel chi-square metric tested for an association between the pretreatment risk group and the PSADT. Logistic regression multivariate analysis was performed to evaluate whether the pretreatment risk group predicted the PSADT. Of the 416 patients, 96 (23%), 194 (47%), and 126 (30%) were categorized as low, intermediate, and high risk, respectively. A total of 92 patients (22%) experienced BF. Of these 92 patients, the PSADT was 3 months or less in 6 (7%), longer than 3 months to less than 6 months in 13 (14%), 6 months to less than 12 months in 35 (36%), and 12 months or longer in 38 (41%). The pretreatment risk group correlated significantly with the PSADT (P = 0.026). Logistic regression analysis revealed that intermediate and high-risk disease was significantly associated with shorter PSADTs (P = 0.039). A significant association between the pretreatment risk group and posttreatment PSADT was demonstrated. Use of this selection criterion at diagnosis for more aggressive treatment appears warranted.


Surveillance of Contagious Equine Metritis: Results of the First 5-Year Period of French Proficiency Tests for Taylorella equigenitalis Detection by Real-Time PCR.
Contagious equine metritis (CEM) detection by PCR is recognized by the European Union according to Commission Implementing Regulation (EU) No 846/2014, and real-time PCR is now recommended by the World Organisation for Animal Health Terrestrial Manual at the same level as the culture method. The present study highlights the creation of an efficient network of approved laboratories in France in 2017 for CEM detection by real-time PCR. The network currently consists of 20 laboratories. A first proficiency test (PT) was organized by the national reference laboratory for CEM in 2017 to evaluate the performance of the early network, followed by annual proficiency tests organized for ongoing periodic assessment of network performance. Results of the 5 PTs organized from 2017 to 2021 are presented, during which 5 real-time PCRs and 3 DNA extraction methods were used. Overall, 99.20% of the qualitative data corresponded to expected results and the R-squared of global DNA amplification calculated for each PT varied from 0.728 to 0.899. DNA extraction is also an important step in the analytical process, and results were more favorable with direct lysis compared to column extraction. Focusing on the most commonly used PCR (PCR 1: 86.4% of results) showed lowest cycle threshold values with direct lysis compared to column and magnetic bead extractions, and with magnetic bead extraction compared to column extraction, but neither of these differences were statistically significant.


Therapeutic ERCP in outpatients.
We evaluated the safety of outpatient therapeutic ERCP since most complications are apparent within a few hours. We reviewed 190 patients undergoing planned outpatient therapeutic ERCP from a cohort of 409 consecutive therapeutic ERCP procedures. Patients were selected for outpatient therapeutic ERCP based on relative good health and overnight accommodation near our institution. Outpatient therapeutic ERCPs included plastic biliary stent insertion (n = 71), biliary sphincterotomy (45), pancreatic stent insertion (28), Wallstent insertion (19), biliary balloon or catheter dilation (10), pancreatic balloon or catheter dilation (8), biliary stone extraction with prior sphincterotomy (7), pancreatic sphincterotomy (5), and duodenal ampullectomy (1). Admission was necessary in 31 (16%) because of complications in 22 (11.6%) and observation of post-ERCP symptoms in 9. Twenty-six (13%) of these patients were admitted directly from the endoscopy unit recovery room and 5 (3%) from home after a median interval of 24 hours following discharge (range 5 to 48 hours). Reasons for admission were pancreatitis in 17, hemorrhage in 3, cholangitis in 3, endoscopic but not clinical hemorrhage in 4, pain in 4, and vomiting in 1. Of the patients who were admitted from home, 3 had pancreatitis (following sphincterotomy in 1, pancreatic stenting in 1, pancreatic balloon dilation in 1) and 2 had hemorrhage (postsphincterotomy in 1 and ampullectomy in 1). In comparison, of the 219 consecutive inpatients undergoing therapeutic ERCP, 28 (13%) developed complications with 1 (0.4%) death. A policy of selective outpatient therapeutic ERCP, with admission reserved for those with established or suspected complication, appears to be safe and reduces health care costs.


Germline and Tumor Sequencing as a Diagnostic Tool To Resolve Suspected Lynch Syndrome.
Patients in whom mismatch repair (MMR)-deficient cancer develops in the absence of pathogenic variants of germline MMR genes or somatic hypermethylation of the MLH1 gene promoter are classified as having suspected Lynch syndrome (SLS). Germline whole-genome sequencing (WGS) and targeted and genome-wide tumor sequencing were applied to identify the underlying cause of tumor MMR deficiency in SLS. Germline WGS was performed on samples from 14 cancer-affected patients with SLS, including two sets of first-degree relatives. MMR genes were assessed for germline pathogenic variants, including complex structural rearrangements and noncoding variants. Tumor tissue was assessed for somatic MMR gene mutations using targeted, whole-exome sequencing or WGS. Germline WGS identified pathogenic MMR variants in 3 of the 14 cases (21.4%), including a 9.5-megabase inversion disrupting MSH2 in a mother and daughter. Excluding these 3 MMR carriers, tumor sequencing identified at least two somatic MMR gene mutations in 8 of 11 tumors tested (72.7%). In a second mother-daughter pair, a somatic cause of tumor MMR deficiency was supported by the presence of double somatic MSH2 mutations in their respective tumors. More than 70% of SLS cases had double somatic MMR mutations in the absence of germline pathogenic variants in the MMR or other DNA repair-related genes on WGS, and, therefore, were confidently assigned a noninherited cause of tumor MMR deficiency.


Safety of thoracoscopic lobectomy in locally advanced lung cancer.
Thoracoscopic lobectomy is well established for the treatment of early non-small cell lung cancer (NSCLC). Its safety and efficacy for advanced-stage disease remain uncertain. Between January 1, 2002, and July 31, 2007, a total of 125 patients were evaluated for thoracoscopic lobectomy for advanced NSCLC. Thoracoscopic lobectomy was completed in 73 patients. Eleven patients were excluded for extensive chest wall involvement. Open resection was performed in 41 patients, with 19 planned thoracotomies and 22 conversions from an initial thoracoscopic approach. Median operative blood loss, operation time, major complications, and hospital length of stay were all similar for patients undergoing thoracoscopic and open resection. A higher percentage of patients who underwent thoracoscopic lobectomy were able to receive adjuvant therapy compared to the open group (37.2% vs. 5.2%; P = 0.006). The differences between the thoracoscopic and open groups in overall survival (43.7 vs. 22.9 months; P = 0.59) and disease-free survival (34.7 vs. 16.7 months; P = 0.84) were not significant. Thoracoscopic lobectomy for advanced-stage NSCLC can be performed safely, with results equivalent to open techniques. With continued experience, lower morbidity with resections performed for advanced-stage disease by video-assisted thoracoscopic surgery will be expected, similar to that observed with early-stage disease. This is particularly important given the large number of frail patients with advanced-stage disease who require multimodal therapy.


CT findings of pulmonary cysts.
Pulmonary cysts are thin-walled radiolucent lesions that may appear in a variety of uncommon disorders known as diffuse cystic lung diseases (DCLD) that essentially includes lymphangioleiomyomatosis (LAM), Langerhans cell histiocytosis (LCH), lymphocytic interstitial pneumonia (LIP), Pneumocystis jiroveci pneumonia (PJP), and Birt-Hogg-Dubé syndrome (BHDS). Moreover, they have been reported in several cases of coronavirus disease 2019 (COVID-19). The purpose of this review is to provide a practical approach for evaluating lung cysts when encountered on CT. We describe the imaging findings of DLCD emphasising their differences in terms of shape and distribution of the cysts, as well as their association with other findings such as nodules or ground-glass opacities, which may help in making a confident diagnosis. We also discuss the link between pulmonary cysts and COVID-19.


Diagnostic value of a medical algorithm for investigation of perioperative hypersensitivity reactions.
Evaluation of perioperative hypersensitivity (POH) is challenging, and accurate screening tools are needed to optimize the diagnostic process. We aimed to assess and validate the diagnostic value of a published algorithm (using tryptase and clinical presentation) to identify appropriate individuals for further testing for IgE-mediated POH. We analysed the clinical presentation (tryptase elevation, cardiovascular, respiratory, skin involvement) of patients proceeding to testing for possible IgE-mediated POH at a single tertiary referral centre, relative to subsequent skin testing and specific IgE results. Clinical presentations by drug class were also determined. In 293 consecutive patients, the use of a published algorithm based on one or more of; (i) defined increase in serum tryptase, (ii) involvement of at least two-organ systems, or (iii) presentation with new urticaria and/or angioedema; was highly sensitive [98.8% (CI95: 95.7-99.9%)] but less specific [34.6% (CI95: 25.7-44.4%)] in identifying patients testing positive on skin testing and/or specific IgE. Presentation with cardiovascular symptoms was also sensitive [89.8%(CI95: 84.2-94.0%)], while the combination of respiratory symptoms and increased tryptase was most specific [85.9%(CI95:76.6-92.5%)]. Respiratory involvement was more common in neuromuscular blocking agent allergy, while urticaria/angioedema was more common in antibiotic allergy. The published algorithm (of tryptase rise, two-organ involvement or new urticaria/angioedema) is highly sensitive, and appropriate as a screening tool to identify patients suitable for testing for IgE-mediated POH.


A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia.
To compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) with that of a low-dose combined oral contraceptive (COC) in reducing fibroid-related menorrhagia. In this single-center, open, randomized clinical trial, 58 women with menorrhagia who desired contraception were randomized to receive a LNG-IUS or COC. The outcomes included treatment failure, defined as the need for another treatment; menstrual blood loss (MBL) by the alkaline hematin method and a pictorial assessment chart (PBAC); hemoglobin levels; and "lost days." Treatment failed in 6 women (23.1%) in the LNG-IUS group and 11 (37.9%) in the COC group, for a hazard ratio of 0.46 (95% CI, 0.17-1.17, P=0.101). Using the alkaline hematin test, the reduction of MBL was significantly greater in the LNG-IUS group (90.9% ± 12.8% vs 13.4% ± 11.1%; P<0.001). Using PBAC scores, the reduction was also significantly greater in the LNG-IUS group (88.0% ± 16.5% vs 53.5% ± 5 1.2%; P=0.02). Moreover, hemoglobin levels increased from 9.7 ± 1.9g/dL to 11.7 ± 1.2g/dL (P<0.001) and lost days decreased from 8.2 ± 3.3 days to 1.3 ± 1.5 days (P=0.003) in the LNG-IUS group. Although the rate of treatment failure was similar in both groups, the LNG-IUS was more effective in reducing MBL than the COC in women with fibroid-related menorrhagia.


Comparative study of flex heart rate in colombian children and in pregnant, lactating, and non-pregnant, nonlactating women.
The heart rate (HR) value employed to separate resting and active portions of the calibration curves used to estimate energy expenditure (EE) from minute-by-minute HR recordings is called the flex-HR. The present study has characterized it, the resting HR and the average daily HR during the awake portion of the day (12-14 h) by comparing age, gender and nutritional status effects related to measured maximum oxygen consumption (V̇ O 2 max; ml/min/kg body weight)in school-aged Colombian children (145 boys and 132 girls), 6-16 years of age. The same HR variables have been individually measured in nutritionally normal, nonpregnant, nonlactating (NPNL; n = 48), pregnant (n = 26), and lactating (n = 18) women, 19-43 years of age, on three occasions separated by 3 months. In general, the flex-HR followed the differences observed in resting and average daily HRs. All three values decreased with age in children, were higher in girls than boys, and did not exhibit differences between nutritionally normal and undernourished children. All three HRs had a statistically significant negative relationship with V̇ O 2 max in boys but not in girls. NPNL and lactating women showed no significant change in the mean values of the repeated HR measurements but exhibited maximum individual differences of flex-HR of -56 to +42 beats/min. Pregnant women had higher HRs in all 3 rounds of measurement compared to NPNL subjects. The data support the generalization that the flex-HR method of estimating EE is appropriate in groups of subjects but not in individuals, and that individual calibration of subjects close to the time of application to the making of EE measurements is an important feature of its use. Am. J. Hum. Biol. 9:647-657, 1997. © Wiley-Liss, Inc.


A bovine herpesvirus type 1 mutant virus with truncated glycoprotein E cytoplasmic tail has defective anterograde neuronal transport in rabbit dorsal root ganglia primary neuronal cultures in a microfluidic chamber system.
Bovine herpesvirus type 1 (BHV-1) is an important component of the bovine respiratory disease complex (BRDC) in cattle. Following primary intranasal and ocular infection of cattle, BHV-1 establishes lifelong latent infection in trigeminal ganglia (TG). Upon reactivation from latency, the virus is transported from neuronal cell bodies in the TG to projected nerve endings in nose and cornea of latently infected cattle where the virus shedding occurs. This property of BHV-1 plays a significant role in the pathogenesis of BRDC and maintenance of BHV-1 in the cattle population. Recently, we have reported that a glycoprotein E (gE) cytoplasmic tail-truncated BHV-1 (BHV-1 gEAm453) did not reactivate from latency and was not shed in the nasal and ocular secretions of calves and rabbits. Here we describe the methods to establish rabbit primary dorsal root ganglia (DRG) neuron cultures in a microfluidic chamber system and to characterize in vitro anterograde and retrograde axonal transport properties of BHV-1 gE-deleted and BHV-1 cytoplasmic tail-truncated gEAm453 mutant viruses relative to BHV-1 gEAm453-rescued/wild-type viruses. The results clearly demonstrated that whereas the BHV-1 gE-deleted, BHV-1 gEAm453, and BHV-1 gEAm453-rescued/wild-type viruses were transported equally efficiently in the retrograde direction, only the BHV-1 gEAm453-rescued/wild-type virus was transported anterogradely. Therefore, we have concluded that sequences within the BHV-1 gE cytoplasmic tail are essential for anterograde axonal transport and that primary rabbit DRG neuronal cultures in the microfluidic chambers are suitable for BHV-1 neuronal transport studies.


Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers.
Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.


Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase.
Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multiple myeloma, disrupts monoclonal protein trafficking and induces apoptosis. We have recently reported a series of isoprenoid triazole bisphosphonates and have demonstrated that a 3:1 mixture of homogeranyl and homoneryl isomers potently, and in a synergistic manner, inhibits GGDPS. We now present the synthesis and biological evaluation of a novel series of bishomoisoprenoid triazoles which furthers our understanding of the structure-function relationship of this class. These studies demonstrate the importance of chain length and olefin stereochemistry on inhibitory activity.


Discovery of New Potent Positive Allosteric Modulators of Dopamine D2 Receptors: Insights into the Bioisosteric Replacement of Proline to 3-Furoic Acid in the Melanostatin Neuropeptide.
The control of Parkinson's disease (PD) is challenged by the motor and non-motor fluctuations as well as dyskinesias associated with levodopa long-term therapy. As such, pharmacological alternatives to reduce the reliance on this drug are needed. Melanostatin (MIF-1), a positive allosteric modulator (PAM) of D2 receptors (D2R), is being explored as a novel pharmacological approach focused on D2R potentiation. In this work, 3-furoic acid (3-Fu) was successfully employed as an l-proline (Pro) surrogate, affording two potent MIF-1 analogues, methyl 3-furoyl-l-leucylglycinate (4a) and 3-furoyl-l-leucylglycinamide (6a). In this series, the C-terminal carboxamide moiety was found crucial to enhancing the potency and toxicological profile, yet it is not considered a requisite for the PAM activity. Conformational analysis excludes 4a from adopting the claimed type II β-turn. The discovery and validation of 6a as a lead compound open a new avenue for the development of a novel class of anti-Parkinson therapeutics targeting the D2R.


Outcome of allogeneic stem cell transplantation following reduced-intensity conditioninig regimen in patients with idiopathic myelofibrosis: the g.I.T.m.o. Experience.
Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for myelofibrosis (MI), though limited by a high rate of transplant-related mortality (TRM). In the present study we evaluate the outcome of MI patients undergoing an allogenic SCT after reduced intensity conditioning (RIC) regimens, and the impact of prognostic factors. Fifty two patients were transplanted in 26 Italian centres between 1998 and 2006. We analyzed the influence of patient and disease clinical features before SCT and of transplant procedures on TRM and overall survival (OS) by means of univariate and multivariate analyses. At SCT, median age was 52,5 years (32-68) and 89% of the patients had an intermediate or high Dupriez score. Conditioning regimens were based on fludarabine plus busulphan in 27% of patients, thiotepa plus cyclophosphamide in 46% and miscellaneous drug combinations in the other 27% of cases. Stem cells came from matched sibling donors for 75% of the patients and mismatched sibling or unrelated donors for the remaining 25%. The cumulative incidence of engraftment at day 90 after transplant was 83% (95% CI, 0.87-0.97). The estimated 1-year TRM was 30%. The estimated 3-year event-free-survival (EFS) and OS after hematopoietic SCT was 44% and 38% respectively. In multivariate analysis, an higher leukocyte count and circulating blasts in the peripheral blood before SCT significantly reduced EFS and OS respectively. We conclude that the extension of the disease before transplantation based on the presence of circulating blasts and high leukocyte counts significantly affected the outcome after HSCT.


Versatile tool for the manipulation of electrophoresis chips.
This communication describes a versatile tool allowing standard operations (i.e. washing, pre-conditioning, separation, inner surface modification of the chip channel) with capillary electrophoresis chips. Through currently designed for a chip of maximal dimensions 30 x 60 mm, other formats of the chip require only a minimum adjustment of the equipment, namely setting of the chip sliding rails and adequate arrangement of the exchangeable heads. The application of the tool is demonstrated by the separation of the standard set of inorganic cations.


Gross morphology of the intra-oral rhamphotheca, oropharynx and proximal oesophagus of the emu (Dromaius novaehollandiae).
Information on the gross morphology of the upper digestive tract of ratites is sparse. This is an important region considering that it is the first area for food selection and intake which is vital to the nutrition and growth of the animal and therefore its commercial viability. Twenty-three heads from sub-adult (12-14 months) emus were used to provide a definitive description of the oropharynx and proximal oesophagus. Besides supplying baseline morphological data of veterinary importance, this study also underlines the functional importance of this region. The mandibular and maxillary nails, and serrations on the rostral mandibular tomia, provide the emu with a formidable combination of gripping, tearing and pecking power. The folded oropharyngeal floor allows distention of the dorso-ventrally flattened cavity during eating and drinking. The laryngeal mound performs both respiratory and digestive functions, whereas the distensible proximal oesophagus supports the particular feeding method employed by ratites.


Bioactivity and secretion of interleukin-18 (IL-18) generated by equine and feline IL-18 expression constructs.
Interleukin 18 (IL-18) is a cytokine capable of induction of IFNgamma, granulocyte monocyte-colony stimulating factor (GM-CSF), TNFalpha and IL-1 in immunocompetent cells. Equine and feline plasmid vectors expressing pro-IL-18, mature IL-18 and IL-18 fused to a synthetic signal sequence from human IL-1beta receptor antagonist protein (ILRAP), ILRAP-IL-18, have been generated. In vitro protein expression of these constructs was compared by Western blot analysis. These data demonstrated that ILRAP-IL-18 protein was secreted readily from transfected chinese hamster ovary (CHO) cells. A simple bioassay for human IL-18 was recently described using human myelomonocytic KG-1 cells, which produce human IFNgamma in response to human IL-18 in a dose dependent manner (Konishi et al., 1997). We demonstrated bioactivity of equine and feline IL-18 protein in transfection products of CHO cells using this assay. Bioactivity of ILRAP-IL-18 protein was demonstrated in the culture medium of transfected CHO cells. These data imply that the ILRAP-IL-18 construct shows potential for use in vivo, where cell secretion of protein is crucial.


Fighting COVID-19 with the team of 5 million: Aotearoa New Zealand government communication during the 2020 lockdown.
Aotearoa New Zealand's response to the COVID-19 pandemic is considered one of the best in the world. A major component of the government response was the communication of public health measures. In this paper, we approach Prime Minister Jacinda Ardern's daily press briefings with the Director-General of Health, Ashley Bloomfield as a case study of government communication during a public health crisis. A reflexive thematic analysis leads us to identify three key themes: 1) open, honest and straightforward communication; 2) distinctive and motivational language; and 3) expressions of care. Situating our findings in the fields of crisis communication, science communication and psychology, we argue that the messages presented in the 2020 daily briefings supported the New Zealand Government's COVID-19 elimination strategy through building trust with the audience and framing the 'lockdown' as an urgent, collective and meaningful cause, mobilising New Zealanders to support public health measures.