Real-world implementation of normothermic machine perfusion: A detailed analysis of intraoperative and early postoperative impact.
Outcome data for the great majority of liver normothermic machine perfusion (NMP) cases derive from the strict confines of clinical trials. Detailed specifics regarding the intraoperative and early postoperative impact of NMP on reperfusion injury and its sequelae during real-world use of this emerging technology remain largely unavailable. We analyzed transplants performed in a 3-month pilot period during which surgeons invoked commercial NMP at their discretion. Living donor, multi-organ, and hypothermic machine perfusion transplants were excluded. Intraoperatively, NMP (n = 24) compared to static cold storage (n = 25) recipients required less peri-reperfusion bolus epinephrine (0 vs. 60 μg; p < .001) and post-reperfusion fresh frozen plasma (2.5 vs. 7.0 units; p = .0069), platelets (.0 vs. 2.0 units; p = .042), and hemostatic agents (0% vs. 24%; p = .010). Time from incision to venous reperfusion did not differ (3.6 vs. 3.1; p = .095) but time from venous reperfusion to surgery end was shorter for NMP recipients (2.3 vs. 2.8 h; p = .0045). Postoperatively, NMP recipients required fewer red blood cell (1.0 vs. 4.0 units; p = .0083) and fresh frozen plasma (4.0 vs. 7.0 units; p = .046) transfusions, had shorter intensive care unit stays (33.5 vs. 58.4 h; p = .012), and experienced less early allograft dysfunction according to both the Model for Early Allograft Function Score (3.4 vs. 5.0; p = .0047) and peak AST within 10 days of transplant (619 vs. 1,181 U/L; p = .036). Liver acceptance for the corresponding recipient was conditional on NMP use for 63% (15/24) of cases. Real-world NMP use was associated with significantly lower intensity of reperfusion injury and intraoperative and postoperative care that may translate into patient benefit.


Methotrexate as single therapy in Crohn's disease: is its long-term efficacy limited?
To determine the efficacy and patient tolerance of parenteral methotrexate in the treatment of Crohn's disease at a dose of 25mg per week for three months, then at 15-25mg per week as maintenance therapy. Thirty-five patients (27 women, eight men; mean age 36 years) with steroid-dependent Crohn's disease were included in the study after failure of azathioprine in 34 cases. Clinical remission was defined as a Harvey-Bradshaw disease-activity index less than or equal to 4 and complete weaning from steroids. At the end of the three-month induction treatment, the Harvey-Bradshaw index decreased significantly (4.6+/-2.9 versus 9.4+/-5.2; P=0.0001), as did serum CRP (24+/-27 versus 43+/-45 mg/L; P=0.01) and prednisone dose (5.63+/-7.3 versus 21.1+/-18.7 mg/L; P=0.00001). The mean maintenance dose of methotrexate was 20.3+/-3.8 mg per week. The rate of clinical remission was 50% at three months and 28% at one year and two years. Nine patients had an adverse event attributed to methotrexate that led to drug withdrawal in six cases (17%). Our findings suggest that, for steroid-dependent Crohn's disease which has failed to respond to thiopurines, long-term methotrexate remains effective in fewer than one in three patients.


Cetylpyridinium chloride direct spray treatments reduce Salmonella on cantaloupe rough surfaces.
Cetylpyridinium chloride (CPC) solutions (0, 0.5, or 1.0%) were applied to cantaloupe ("Athena" and "Hale's Best Jumbo" cultivars) rind plugs, either before or after inoculation with a broth culture of Salmonella Michigan (109 CFU/mL) and held at 37°C for 1 or 24 hr. Rind plugs were diluted, shaken, and sonicated, and solutions were enumerated. Texture quality and color were evaluated over 14 days storage at 4°C after 0 and 1% CPC spray applications. A 0.5 or 1.0% (vol/vol) application of CPC after Salmonella reduced the pathogen levels between 2.34 log CFU/mL and 5.16 log CFU/mL in comparison to the control (p < .01). No differences were observed in the firmness and color of 1% CPC treated cantaloupes. Salmonella concentrations on cantaloupes, treated with 1.0% CPC, were lower after 1 hr storage as compared to 24 hr. And, Salmonella on "Athena" surfaces were more susceptible to CPC spray treatments than on "Hale's Best Jumbo." Cetylpyridinium chloride (CPC) is the active ingredient of some antiseptic oral mouth rinses, and has a broad antimicrobial spectrum with a rapid bactericidal effect on gram-positive pathogens. The spray application of CPC solutions to cantaloupe may reduce the level of Salmonella surface contamination during production from irrigation water and manure fertilizers and, during food processing by contaminated equipment and food handlers. Since the surfaces of cantaloupes are highly rough or irregular, bacteria can easily attach to these surfaces and become difficult to remove. Appropriate postharvest washing and sanitizing procedures are needed that can help control Salmonella and other pathogens on melons, especially on cantaloupes with nested surfaces. A direct surface spray application of CPC may be an alternative antimicrobial postharvest treatment to reduce pathogen contamination of cantaloupe melons, while providing an alternative to chlorine-based solutions.


The Journey to Establish CGRP as a Migraine Target: A Retrospective View.
In this retrospective, Dr. Lars Edvinsson recounts early steps and milestones in our understanding of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigeminovascular system and its role in migraine. The discovery of the presence and function of CGRP and other neuropeptides in the cerebral vasculature and its sensory innervation is described. He relates the seminal finding that CGRP is uniquely released during migraine and the journey to develop blockers of CGRP effects. Now, over 30 years since its discovery, CGRP has become the target for a number of promising novel treatments for migraine patients.


Primary mediastinal lymphoma in adults.
The incidence of primary mediastinal lymphoma in adults was investigated in 184 patients with non-Hodgkin's lymphoma. This entity was defined as disease within the mediastinum in patients who presented with symptoms due to an enlarging mediastinal mass. Of 184 patients, 17 presented with primary mediastinal lymphoma. All had a diffuse histologic pattern. The most common pathologic type was poorly differentiated lymphocytic lymphoma, diffuse (PDL-D), (11 cases). In nine of these 11 cases the patients had tumors of convoluted lymphocytes. The presentation was rapid in onset, with heart failure, pericarditis, dyspnea and superior vena caval syndrome predominating. Eleven of the 17 were clinical stage I or II, but eight of these had widespread disease on pathologic staging or rapid dissemination soon after diagnosis. In conclusion (1) primary mediastinal lymphoma is always diffuse in histology. (2) The most frequent pathologic type is PDL-D, with convoluted morphology. (3) Compression of vital intra-thoracic structures is common. (4) Although seemingly localized at presentation, this entity usually implies disseminated disease.


Manganese homeostasis and transport.
The review addresses issues pertinent to Mn accumulation and its mechanisms of transport, its neurotoxicity and mechanisms of neurodegeneration. The role of mitochondria and glia in this process is emphasized. We also discuss gene x environment interactions, focusing on the interplay between genes linked to Parkinson's disease (PD) and sensitivity to Mn.


Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants.
The presence of microorganisms in gastric fluid in neonates at birth is postulated to reflect antenatal infection and also to be associated with the development of bronchopulmonary dysplasia (BPD). A logistic regression analysis, after controlling for other risk factors, indicated that Ureaplasma-positive infants were not at increased risk for moderate/severe BPD (adjusted odds ratio (OR): 2.58, 95% confidence interval (CI): 0.57-6.89, P = 0.12). However, the association between the presence of Ureaplasma species and the risk for moderate/severe BPD increased significantly in infants on mechanical ventilation (MV) ≥2 wk (adjusted OR: 4.17, 95% CI: 1.62-44.1, P = 0.009). An analysis using a lung injury marker indicated that Ureaplasma-positive infants with MV ≥2 wk, but not other infants, showed higher serum KL-6 levels in samples taken from cord blood, and that KL-6 levels increased time-dependently up to 4 wk of age. Antenatal exposure to Ureaplasma species induces lung injury prior to birth and synergistically contributes to the development of BPD in infants requiring prolonged MV (≥2 wk). We recovered gastric fluid specimens from 122 infants with gestational age (GA) <29 wk or birth weight <1,000 g to investigate whether these microorganisms influence respiratory outcome of BPD. A PCR analysis was used to detect urease and 16S ribosomal RNA (rRNA) genes to classify neonates into Ureaplasma-positive or Ureaplasma-negative infants.


Laryngoscopy findings and histological results in a rabbit gastroesophageal reflux model.
The role of lower esophageal sphincter (LES) in laryngopharyngeal reflux is controversial. In this study, we used an animal model to investigate the association between LES dysfunction and reflux laryngitis. Twelve healthy New Zealand albino rabbits (2.5-3.5 kg) were utilized in this study. The animals were divided into two groups. Eight rabbits underwent total cardiomyectomy to induce reflux, and the remaining four rabbits underwent a control sham operation. A laryngoscopy and a 24-hour intra-esophageal pH-metry were performed prior to surgery and again 2 and 8 weeks postsurgery. After the final laryngoscopy, all animals were sacrificed to obtain histological results. Total cardiomyectomy significantly increased the reflux index, the duration of the longest reflux episode and the total number of episodes that occurred in 24 h postsurgery. No significant difference was observed in the reflux finding score (RFS) between preoperative and 2-week postoperative rabbits (P = 0.11). But there was a statistically significant change in the RFS before and 8 weeks after the induction of reflux from 4.6 ± 0.9 to 8.3 ± 3.6 (P = 0.02). Submucous gland hyperplasia and inflammation were significantly increased in the reflux group compared to the control group. The results of this study suggest that chronic lower esophageal sphincter dysfunction is associated with reflux laryngitis in rabbits.


Continuous epicardial echocardiographic assessment of postoperative left ventricular function.
An ultrasound transducer which is sutured to the heart at operation and removal percutaneously has been developed and tested in 20 animals. The potential of this device to monitor cardiac function was measured by simultaneously recording 67 left ventricular angiograms and echograms over a wide range of hemodynamic function. In addition, the reproducibility of the data obtained from the transducer and the safety of application and withdrawal were examined. We found highly significant (p less than 0.005) linear correlation between echocardiographic and angiographic measurements of left ventricular end-diastolic volume, end-systolic volume, and ejection fraction. This transducer may provide the means to assess left ventricular size and ejection fraction continuously after cardiac operations in man.


[Preliminary experience of radical retropubic prostatectomy using an endoscopic stapler].
Preliminary experience of radical retropubic prostatectomy using an endoscopic stapler is reported. An endoscopic stapler was applied for ligation and division of the lateral prostatic ligaments and the deep dorsal vein complex during radical retropubic prostatectomy in 8 patients. Procedures with stapler were easily performed and almost always effective for hemostasis. Mean total blood loss was 663 ml, mean 575 ml of autologous blood was given. None of patients was transfused allogeneic blood. These results indicate that an endoscopic stapler may facilitate radical retropubic prostatectomy.


Acculturation and weight change in Asian-American children: Evidence from the ECLS-K:2011.
Despite relatively low rates of overweight and obesity among Asian-American children, disparities exist based on acculturation, socioeconomic status, and Asian ethnicity. The purpose of this study was to examine the association between acculturation and weight change in Asian-American children. Secondary aims were to compare changes by Asian ethnic group and acculturation x socioeconomic status. Participants included 1200 Asian-American children from the Early Childhood Longitudinal Study, Kindergarten Class of 2010-11, a longitudinal study of U.S. children attending kindergarten in 2010-2011. Multinomial logistic regressions were conducted to predict weight change based on body mass indices in kindergarten (spring 2011) and second grade (spring 2013): consistently healthy weight, consistently overweight/obese, healthy weight change, and unhealthy weight change. Models included demographic, household, socioeconomic status, and acculturation measures, specifically mother's English proficiency and percentage of life spent in the U.S. Overall, 72.3% of children were at healthy weights in kindergarten and second grade. Of all Asian ethnic groups, Filipino children had the highest rate of being consistently overweight/obese (24.8%) and the lowest rate of being consistently healthy weight (62.9%). In addition, mother's English proficiency predicted unhealthy weight change (OR: 0.83; 95% CI: 0.75-0.92) and healthy weight change (OR: 0.75; 95% CI: 0.65-0.86), relative to "consistently healthy weight." English proficiency also predicted being consistently overweight/obese for children with less educated mothers. Findings enhance our understanding of obesity disparities within Asian Americans and highlight the need to disaggregate the population. Obesity interventions are needed for Filipino children and families with low socioeconomic status but high English proficiency.


Effect of anti-DR5 and chemotherapy on basal-like breast cancer.
The purpose is to evaluate sensitivity of basal-like breast cancer to treatment with anti-DR5 alone and in combination with chemotherapy. Cytotoxicity of TRA-8 anti-DR5 alone and in combination with doxorubicin or paclitaxel was examined. The role of a DR5-associated molecule (DDX3) in the regulation of apoptosis by recruitment of cIAP1 to the DR5/DDX3 complex was studied. SUM159 and 2LMP orthotopic xenografts were treated with TRA-8 alone and in combination with Abraxane or doxorubicin, and tumor growth inhibition determined. Diffusion-weighted magnetic resonance imaging was used to monitor early tumor response. The majority (12/15) of basal-like cell lines were very sensitive to TRA-8-induced cytotoxicity (IC(50) values of 1.0-49 ng/ml). In contrast, 8/11 luminal or HER2-positive cell lines were resistant (IC(50) > 1,000 ng/ml). Enhanced killing of basal-like cell lines was produced by combination treatment with TRA-8 and doxorubicin. Majority of basal cell lines expressed lower levels of DR5-associated DDX3 and cIAP1 than luminal and HER2-positive cell lines. TRA-8 inhibited growth of basal xenografts and produced 20% complete 2LMP tumor regressions. TRA-8 and chemotherapy produced greater 2LMP growth inhibition than either alone. An increase in apparent diffusion coefficient in 2LMP tumors was measured in a week of therapy with TRA-8 and Abraxane. Basal-like cell lines were more sensitive to TRA-8-mediated cytotoxicity than HER2-over-expressing and luminal cell lines, and chemotherapy enhanced cytotoxicity. High sensitivity of basal cells to TRA-8 correlated with low expression of DR5/DDX3/cIAP1 complex. Treatment with TRA-8 and chemotherapy may be an effective therapy for basal-like breast cancer.


What is the optimal duration for a ROAT? The experience of the French Dermatology and Allergology group (DAG).
The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week. The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT. A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty-nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days. According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product.


Cognitive impairment in older adults with heart failure: prevalence, documentation, and impact on outcomes.
Despite the fact that 80% of patients with heart failure are aged more than 65 years, recognition of cognitive impairment by physicians in this population has received relatively little attention. The current study evaluated physician documentation (as a measure of recognition) of cognitive impairment at the time of discharge in a cohort of older adults hospitalized for heart failure. We performed a prospective cohort study of older adults hospitalized with a primary diagnosis of heart failure. Cognitive status was evaluated with the Folstein Mini-Mental State Examination at the time of hospitalization. A score of 21 to 24 was used to indicate mild cognitive impairment, and a score of ≤20 was used to indicate moderate to severe impairment. To evaluate physician documentation of cognitive impairment, we used a standardized form with a targeted keyword strategy to review hospital discharge summaries. We calculated the proportion of patients with cognitive impairment documented as such by physicians and compared characteristics between groups with and without documented cognitive impairment. We then analyzed the association of cognitive impairment and documentation of cognitive impairment with 6-month mortality or readmission using Cox proportional hazards regression. A total of 282 patients completed the cognitive assessment. Their mean age was 80 years of age, 18.8% were nonwhite, and 53.2% were female. Cognitive impairment was present in 132 of 282 patients (46.8% overall; 25.2% mild, 21.6% moderate-severe). Among those with cognitive impairment, 30 of 132 (22.7%) were documented as such by physicians. Compared with patients whose cognitive impairment was documented by physicians, those whose impairment was not documented were younger (81.3 vs 85.2 years, P<.05) and had less severe impairment (median Mini-Mental State Examination score 22.0 vs 18.0, P<.01). After multivariable adjustment, patients whose cognitive impairment was not documented were significantly more likely to experience 6-month mortality or hospital readmission than patients without cognitive impairment. Cognitive impairment is common in older adults hospitalized for heart failure, yet it is frequently not documented by physicians. Implementation of strategies to improve recognition and documentation of cognitive impairment may improve the care of these patients, particularly at the time of hospital discharge.


Prognosis for children with neuroblastoma presenting with paralysis.
Since 1947, we have treated 19 children with neuroblastoma whose first symptoms were paralysis or weakness of an extremity, and/or incontinence due to tumor in the spinal canal. In 18 patients, the spine tumor was part of a dumbbell tumor which was present in the adjacent paravertebral area and in one, no extraspinal tumor was found. Aggressive treatment was employed for all. In 17 children, the intraspinal tumor was treated by laminectomy and irradiation with and without chemotherapy. Radiation and chemotherapy were used for two. The extraspinal tumor was excised totally in six and partially in six. All 12 children received postoperative radiation and chemotherapy. In 6 children, the extraspinal tumor was treated only with radiation and chemotherapy. Nine of 19 children are alive without evidence of neuroblastoma. Thirteen patients showed either partial (6) or full (7) neurologic recovery. Survival was related to the child's age at diagnosis and the extent of disease. While 8 of 9 children under 1 yr of age survived, only 1 of 10 children over 1 yr survived. None of the 5 children with Stage IV disease at diagnosis could be saved. The degree and frequency of neurologic recovery were greatest in children whose neurologic symptoms had been present the shortest times and were equal among those who survived and those who died. The outlook for children who became paralyzed by neuroblastoma is not hopeless; therapy aimed at saving life or neurologic function is both worthwhile and rewarding.


Carbonic anhydrase inhibitors. Inhibition of red blood cell ostrich (Struthio camelus) carbonic anhydrase with a series of aromatic and heterocyclic sulfonamides.
The purification of red blood cell carbonic anhydrase (CA, EC 126.96.36.199) from ostrich (scCA) blood is reported, as well as an inhibition study of this enzyme with a series of aromatic and heterocylic sulfonamides. The ostrich enzyme showed a high activity, comparable to that of the human isozyme II, with kcat, of 1.2 x 10(6) s(-1) and kcat/KM of 1.8 x 10(7) M(-1)s(-1), and an inhibition profile quite different from that of the human red blood cell cytosolic isozymes hCA I and II. scCA has generally a lower affinity for sulfonamide inhibitors as compared to hCA I and II. The only sulfonamide which behaved as a very potent inhibitor of this enzyme was ethoxzolamide (KI = 3.9 nM) whereas acetazolamide and sulfanilamide behaved as weaker inhibitors (inhibition constants in the range 303-570 nM). Several other aromatic and heterocyclic sulfonamides, mostly derivatives of sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide, showed good affinities for the ostrich enzyme, with KI values in the range 25-72 nM.


Highly colloidally stable trimodal 125I-radiolabeled PEG-neridronate-coated upconversion/magnetic bioimaging nanoprobes.
"All-in-one" multifunctional nanomaterials, which can be visualized simultaneously by several imaging techniques, are required for the efficient diagnosis and treatment of many serious diseases. This report addresses the design and synthesis of upconversion magnetic NaGdF4:Yb3+/Er3+(Tm3+) nanoparticles by an oleic acid-stabilized high-temperature coprecipitation of lanthanide precursors in octadec-1-ene. The nanoparticles, which emit visible or UV light under near-infrared (NIR) irradiation, were modified by in-house synthesized PEG-neridronate to facilitate their dispersibility and colloidal stability in water and bioanalytically relevant phosphate buffered saline (PBS). The cytotoxicity of the nanoparticles was determined using HeLa cells and human fibroblasts (HF). Subsequently, the particles were modified by Bolton-Hunter-neridronate and radiolabeled by 125I to monitor their biodistribution in mice using single-photon emission computed tomography (SPECT). The upconversion and the paramagnetic properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles were evaluated by photoluminescence, magnetic resonance (MR) relaxometry, and magnetic resonance imaging (MRI) with 1 T and 4.7 T preclinical scanners. MRI data were obtained on phantoms with different particle concentrations and during pilot long-time in vivo observations of a mouse model. The biological and physicochemical properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles make them promising as a trimodal optical/MRI/SPECT bioimaging and theranostic nanoprobe for experimental medicine.


Using surveillance and economic data to make informed decisions about rotavirus vaccine introduction.
While rotavirus vaccines are available, safe, and effective, many countries are not yet widely using these vaccines. Surveillance for rotavirus disease and potential vaccine adverse events is critical for country decision making about rotavirus vaccine. This special issue shares rotavirus and intussusception disease surveillance data and rotavirus vaccine cost-effectiveness analyses from countries that have yet to introduce rotavirus vaccines into their routine infant immunization programs. The studies highlight the substantial burden of rotavirus disease and the cost-effectiveness of rotavirus vaccine in a broad set of countries without rotavirus vaccine in their routine immunization programs.


Antibiotics do not reduce toothache caused by irreversible pulpitis. Are systematic antibiotics effective in providing pain relief in people who have irreversible pulpitis?
Cochrane Oral Health Group Trials Register and the Pain, Palliative Care and Supportive Care Group Trials Register, the Cochrane Central Register of Controlled Trials, Medline and Embase. Randomised controlled trials (RCT) were included that involved patients over the age of 18 years who had presented with a single tooth with a clinical diagnosis of irreversible pulpitis. Abstracts of studies were independently assessed by two reviewers. The primary outcome was patient-reported pain (intensity/duration) and pain relief measured on a categorical scale in the preoperative phase of irreversible pulpitis. Secondary outcomes were type, dose and frequency of medication required for pain relief. Only one trial was included so pooling of data from studies was not possible and a descriptive summary is presented. One trial of 40 participants was included. There was a close parallel distribution of the pain ratings in both the intervention and placebo groups over the 7-day study period. The between-group differences in sum pain intensity differences for the penicillin group were 6.0+/-10.5, and for placebo 6.0+/-9.5 (P=0.776; differences assessed by Mann-Whitney-Wilcoxon test considered to be statistically significant at P=0.05). The sum pain percussion intensity differences for the penicillin group were 3.5+/-7.5 and placebo 2.0+/-7.0 (P=0.290). There was no significant difference in the mean total number of ibuprofen tablets (P=0.839) and acetaminophen tablets (P=0.325) taken for pain relief in either group over the study period. The administration of penicillin over placebo did not appear to significantly reduce the quantity of analgesic medication taken (P=0.05) for irreversible pulpitis. This review based on one methodologically sound but low-powered small sample trial, provides some evidence that there is no significant difference in pain relief between individuals who had untreated irreversible pulpitis who did or did not take antibiotics in addition to analgesics.


Health of children conceived after preimplantation genetic diagnosis: a preliminary outcome study.
A preliminary study was conducted on health of children conceived after preimplantation genetic screening and diagnosis (PGD). Forty-nine children were assessed with 66 matched naturally conceived (NC) controls. Primary outcome was neurodevelopmental screening, and secondary outcomes were evidence of other health problems and assessment of parent-child relationships. Study and control children were well matched across relevant socio-demographic variables. Growth parameters at mean age 18 months were normal. The mean Griffiths quotient was 102.7 (+/-13.1) (PGD) and 103.3 (+/-12.8) (NC), both of which were within the normal range, and did not differ significantly. PGD cases were more likely to be lighter, at <2500 g (12 children, 24.5% versus one child 1.5%, P < 0.0001) and born earlier than controls (38.2 +/- 2.6 versus 40.0 +/- 1.4 weeks; P < 0.0001), consistent with other similar studies. PGD families showed no evidence of excess stress in their relationship with their child. The PGD group had significantly higher scores on the warmth-affection sub-scale (P = 0.042), and significantly lower scores on the aggression-hostility and rejection sub-scales (P = 0.030) of the questionnaire. The study showed no major ill effects from PGD on the child health. A larger study is needed to confirm the validity of this conclusion.


Three-Dimensionally Printed Patient-Specific Surgical Plates Increase Accuracy of Oncologic Head and Neck Reconstruction Versus Conventional Surgical Plates: A Comparative Study.
Surgeons are pursuing accurate head and neck reconstruction to enhance aesthetic and functional outcomes after oncologic resection. This study aimed to investigate whether accuracy of head and neck reconstruction is improved with the use of three-dimensionally (3D)-printed patient-specific surgical plates compared with conventional plates. In this comparative study, patients were prospectively recruited into the study group (3DJP16) with 3D-printed patient-specific surgical plates. The patients in control group with conventional surgical plates were from a historic cohort in the same unit. The primary end point of the study was the accuracy of head and neck reconstruction. The secondary end points were accuracy of osteotomy, intraoperative blood loss, total operative time, and length of hospital stay. The study recruited of 33 patients, including 17 in the study group and 16 in the control group. The patients' baseline characteristics were similar between the two groups. The absolute distance deviation of the maxilla or mandible was 1.5 ± 0.5 mm in the study group and 2.1 ± 0.7 mm in the control group [mean difference, - 0.7 mm; 95% confidence interval (CI) - 1.1 to - 0.3; p = 0.003], showing superior accuracy of reconstruction for the patients with 3D-printed patient-specific surgical plates. Improved accuracy of reconstruction also was detected in terms of bilateral mandibular angles and bone grafts. Concerning the secondary end points, the accuracy of the osteotomy was similar in the two groups. No difference was found regarding intraoperative blood loss, total operative time, or length of hospital stay. This is the first study to prove that compared with conventional plates, 3D-printed patient-specific surgical plates improve the accuracy of oncologic head and neck reconstruction.


Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles are determined by the disease, patient age, and anti-leukemic treatment.
Heat shock protein (HSP) 70 and HSP90 are released by primary human acute myeloid leukemia (AML) cells during stress-induced spontaneous in vitro apoptosis. The AML cells also show constitutive release of several cytokines and the systemic serum levels of several soluble mediators are altered in patients with untreated AML. In the present study, we have investigated serum levels of HSP70/HSP90 and the serum cytokine profiles of patients with untreated AML and patients receiving AML-stabilizing palliative treatment based on all-trans retinoic acid (ATRA) plus valproic acid. Patients with untreated AML showed increased HSP90 levels and a distinct serum cytokine profile when compared with healthy controls, and low pre-therapy HSP90 levels were associated with a prolonged survival during treatment with ATRA + valproic acid + theophyllin. Hierarchical cluster analysis showed a close association between HSP70, HSP90, IL-1 receptor antagonist (IL-1ra), and hepatocyte growth factor (HGF) levels. Furthermore, disease-stabilizing therapy altered the serum-cytokine profile, but the correlations between HSP70/HSP90/IL-1ra/HGF were maintained only when ATRA + valproic acid were combined with theophyllin but not when combined with cytarabine. We conclude that both HSP levels and serum cytokine profiles are altered and may represent possible therapeutic targets or prognostic markers in human AML.


Control of prosthetic bacterial infection: evaluation of an easily incorporated, tightly bound, silver antibiotic PTFE graft.
Despite the use of prophylactic antibiotics in vascular surgery, prosthetic infection rate remains 2-5%. Antibiotics bound to vascular prostheses can control experimentally induced infection but prolonged antibacterial activity has not been achieved. This study evaluates the in vivo efficacy and antibiotic retention of an easily prepared silver-antibiotic prosthesis. Prostheses were prepared by combining silver with oxacillin or amikacin using an organic solvent. After evaporation of the solvent, the graft was left impregnated with the antibiotic complex. In vivo retention studies were performed by implanting PTFE 110Ag-oxacillin prostheses in four canine abdominal aortas. When prostheses were explanted at 1 week, mean antibiotic retention was found to be 20% of original activity, higher than the mean inhibitory concentration for Staphylococcus aureus. In three groups of five dogs, 20 X 7-mm prostheses of PTFE alone, PTFE silver-oxacillin, or PTFE silver-amikacin were implanted in the abdominal aorta and the grafts were inoculated with 10(7) S. aureus of a known bacteriophage type, in a closed retroperitoneal pocket. The animals were sacrificed at 1 week and the prostheses were excised for quantitative bacterial culture. PFTE silver-oxacillin, and PTFE silver-amikacin prostheses had 1.7 X 10(2) and 2.0 X 10(2) colonies, respectively, significantly less (P less than 0.05) than controls (1.3 X 10(6) colonies). These data suggest that antibiotic prostheses can be easily prepared without binding agents. They retain the bound antibiotic for a prolonged period and are effective in reducing graft infection in a stringent direct contamination model.


Affinity labeling of the ribonucleic acid component adjacent to the peptidyl recognition center of peptidyl transferase in Escherichia coli ribosomes.
N-Iodacetylphenylalanyl-tRNA was used as an affinity label for localizing the RNA components intimately related to the peptidyl transferase activity of Escherichia coli ribosomesmthis analogue could specifically alkylate a unique nucleotide chain of 23-S RNA. The alkylation was strongly enhanced by poly(U), and was dependent on the presence of both 50- and 30-S subunits; Chloramphenicol inhibited the reaction, wheras blasticidin S stimulated it. The alkylated RNA base was found to be adenine. The nucleotide chain attacked by N-iodoacetylphenylalanyl-tRNA seemed to be localized at or near to the peptidyl recognition center of peptidyl transferase.


Correlative study of the incidence of opaque, necrotic and regenerative fibers in Duchenne dystrophy.
We studied the incidence of opaque, necrotic, and regenerative muscle fibers (OFs, NFs, RFs) in muscle biopsies from 21 patients, aged 8 months to 24 years, with Duchenne muscular dystrophy (DMD). OFs varied from case to case with an average rate of 8.3%. NFs and RFs were high in younger patients and decreased with age. The incidence of OFs, NFs, and RFs correlated to patient age with these coefficients: r = -0.38, -0.91, and -0.86. Except for OFs, all correlations were significant (p less than 0.001). There was no significant correlation between the incidence of OFs and NFs in each case of DMD. Considering the results of previous biochemical analysis of single OFs, we suggest that OFs may comprise two types of muscle fibers: (1) pathological muscle fibers to be regarded as precursors of NFs, and (2) muscle fibers undergoing artificial changes.


Stimulated multifrequency Raman scattering of light in a polycrystalline sodium bromate powder.
The observation of multifrequency stimulated Raman scattering of light in a thin powder layer of a gyrotropic crystal of sodium bromate when excited by intense ultrashort pulses of the second optical harmonic (λ = 532 nm) of an yttrium aluminum garnet laser is reported. Five Stokes and anti-Stokes satellites corresponding to the excitation of the intramolecular optical mode of NaBrO3 crystal were present in the recorded spectra. In addition, Raman satellites corresponding to the excitation of lattice modes, as well as their combinations with intramolecular modes, were found in the spectra of stimulated Raman scattering. The prospects of using stimulated Raman scattering spectroscopy for express analysis of gyrotropic media: gyrotropic polycrystals, crystalline amino acids, proteins, DNA, etc. have been established.


Limited brain access for leptin in obesity.
Obesity is a major health problem that contributes to the development of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The current pharmacological therapies for obesity are limited and may have significant side effects. Leptin therapy was shown to effectively cause weight loss in obese rats, however its effectiveness in humans is still under investigation. Obese humans have significantly elevated plasma leptin concentrations compared with lean individuals. Plasma leptin concentrations strongly correlated with percentage of body fat. Leptin concentration in the cerebrospinal fluid (CSF) is correlated, in a nonlinear manner, with plasma leptin levels and body mass index (BMI). The ratio of CSF leptin levels to serum leptin levels was 4 times greater in lean individuals than in obese individuals. One interpretation of this finding is that human obesity could be secondary to a central resistance to leptin action, causing a relative leptin deficiency in the CNS. Six years after the discovery of leptin we still do not have a clear understanding of how leptin accesses its targets in the brain, or whether there is defect in this process in the brain of obese individuals. In this manuscript we will review the different leptin gateways to the brain and the potential sites where a defect in leptin action may be present, as well as some potential clinical implications of leptin. A better understanding of how leptin reaches the brain and how it modulates the release of hypothalamic neuropeptides will be important in understanding the role that leptin plays in the pathophysiology of obesity.


Hydrocarbation chemistry proceeding from nickel carbenes.
Nickel carbene complex 2 [Ni(triphos)C(H)N(H)xylyl]2+(BF4-)2 reacts with alkenes quantitatively and regiospecifically to give the anti-Markovnikov hydrocarbation products. X-ray crystallography shows significant iminium alkyl character of the hydrocarbation products, similar to that observed in parent carbene 2. Mechanistic studies suggest the importance of a "hydride" pathway over "alkene" (metallocycle formation or carbocation) pathways.


Outcomes of Patients with COVID-19 from a Specialized Cancer Care Emergency Room.
Our goal was to identify discrete clinical characteristics associated with safe discharge from an emergency department/urgent care for patients with a history of cancer and concurrent COVID-19 infection during the SARS-CoV-2 pandemic and prior to widespread vaccination. We retrospectively analyzed 255 adult patients with a history of cancer who presented to Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center (UCC) from March 1, 2020 to May 31, 2020 with concurrent COVID-19 infection. We evaluated associations between patient characteristics and 30-day mortality from initial emergency department (ED) or urgent care center (UCC) visit and the absence of a severe event within 30 days. External validation was performed on a retrospective data from 29 patients followed at Fred Hutchinson Cancer Research Center that presented to the local emergency department. A late cohort of 108 additional patients at MSKCC from June 1, 2020 to January 31, 2021 was utilized for further validation. In the MSKCC cohort, 30-day mortality and severe event rate was 15% and 32% respectively. Using stepwise regression analysis, elevated BUN and glucose, anemia, and tachypnea were selected as the main predictors of 30-day mortality. Conversely, normal albumin, BUN, calcium, and glucose, neutrophil-lymphocyte ratio <3, lack of (severe) hypoxia, lack of bradycardia or tachypnea, and negative imaging were selected as the main predictors of an uneventful course as defined as a Lack Of a Severe Event within Thirty Days (LOSETD). Utilizing this information, we devised a tool to predict 30-day mortality and LOSETD which achieved an area under the operating curve (AUC) of 79% and 74% respectively. Similar estimates of AUC were obtained in an external validation cohort. A late cohort at MSKCC was consistent with the prior, albeit with a lower AUC. We identified easily obtainable variables that predict 30-day mortality and the absence of a severe event for patients with a history of cancer and concurrent COVID-19. This has been translated into a bedside tool that the clinician may utilize to assist disposition of this group of patients from the emergency department or urgent care setting.


The everlasting trial of strength and patience': transitions in home care nursing as narrated by patients and family members.
The aim of this study was to describe and interpret patients' and their family members' lived experiences of caring at home. Twelve tape-recorded narratives, with seven patients and five family members, were interpreted in accordance with a phenomenological-hermeneutic method inspired by Ricoeur. The findings revealed life situations where natural caring was changed into patient-care-giver relations and the home became a public room. The patients had to deal with decreased abilities and the family members with adjusting to caring needs. The changes in the life situations were interpreted as long lasting and trying transitions. Implications for nursing and further research are proposed.


Population Pharmacokinetics Study of Nemonoxacin Among Chinese Patients With Moderate Hepatic Impairment.
Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recommendations for patients with hepatic impairment. An open-label, single-dose, parallel group (moderate hepatic impairment group and healthy control group) PK study of nemonoxacin was conducted. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to detect the unchanged nemonoxacin concentration in blood and urine samples. The nonlinear mixed effects modeling tool NONMEN (version 7.3) was used to conduct the population PK analysis. The paired-t test was conducted to compare the PK parameters of the hepatic impairment group and the healthy control group by SPSS (Version 17.0). Ten subjects for each group were enrolled into the PK study. The PK parameters as well as the plasma concentration-time and logarithmic concentration-time profiles after taking a 500-mg single dose of nemonoxacin showed few differences between the two groups (P > 0.05). The mean areas under the plasma concentration vs. time curve from 0 to 72 h (AUC0-72 h) of the moderate hepatic impairment group and the healthy control group in the nemonoxacin PK study were 58.50 (17.30) mg·h/mL and 49.74 (10.16) mg·h/mL, respectively, giving a mean (SD) AUC0-72 h ratio of 1.15 (0.42) with a 90% CI of 0.91-1.39. A 3- compartment model was considered to be the best model for the data, especially in fitting the plasma point at low drug concentrations. Covariate analysis indicated that weight affected CL/F, V1/F, and V3/F and that eGFR only affected CL/F in the power function model, while gender affected V3/F in the linear model by forward selection and backward deletion. The population PK parameters of nemonoxacin were evaluated in patients with hepatic impairment. The hepatic function did not have a significant impact on the PK parameters of nemonxacin, but renal function was a meaningful covariate that is consistent with its PK characteristics. In this study, nemonoxacin was well tolerated in the patients with moderate hepatic impairment as well as in the healthy subjects. Based on these data, it is not necessary to consider dose adjustment of nemonoxacin in patients with mild or moderate hepatic impairment. ClinicalTrials.gov identifier: NCT02604498.


Volvulus at the ileocaecal junction in germfree mice.
16 cases of intestinal volvulus were observed in a total of 200 inbred C57BL/6N, GR/N, and DBA/2N germfree mice during the course of 2 years. The volvulus was a twisting of the caecum at the junction of the ileum, caecum and colon, resulting in occlusion and death. In each case the caecum was greatly enlarged. During the same period no intestinal volvulus was seen in 5 other germfree strains or in F1 to F4 generations of identical strains of microflora-associated and conventionalized mice.


An unusual case of cervical diverticulum identified by presence of 3 cavities at diagnostic hysteroscopy.
Herein is presented the case report of a patient who had severe dysmenorrhea since menarche, known right unicornuate uterus with a left rudimentary horn, and recurrent hematometra. Previous hysteroscopic drainage of the hematometra temporarily alleviated the symptoms. At subsequent hysteroscopy, 3 cavities were identified, 2 corresponding to the uterine horns and the other to a cervical diverticulum. Hysteroscopic metroplasty with drainage of the rudimentary horn hematometra provided long-term relief of the symptoms. The diagnosis was verified at diagnostic laparoscopy.


The first plastic produced, but the latest studied in microplastics research: The assessment of leaching, ecotoxicity and bioadhesion of Bakelite microplastics.
Bakelite, the first synthetic plastic, is a rather unexplored material in the field of ecotoxicology, despite its long production and use. The aim of this study was to investigate the ecotoxicity of Bakelite microplastics (before and after leaching) and its leachates on four aquatic organisms: the crustacean Daphnia magna, the plant Lemna minor, the bacterium Allivibrio fischeri and the alga Pseudokirchneriella subcapitata. Bakelite microplastics before and after leaching and leachates affected all organisms, but to varying degrees. Leachates showed increased ecotoxicity to Daphnia magna, while Pseudokirchneriella subcapitata was more affected by particles. For Lemna minor and Allivibrio fischeri, the effects of particles before leaching and leachate were comparable, while the negative effect of particles after leaching was minimal or not present. All leachates were analysed, and phenol and phenol-like compounds were the predominant organics found. In addition, bioadhesion of Bakelite microplastics to the surface of Daphnia magna and Lemna minor was confirmed, but the particles were mainly weakly adhered. Results of this study suggest that, in addition to the recently studied microplastics from consumer products (e.g. from polyethylene and polystyrene), microplastics from industrial plastics such as Bakelite may be of increasing concern, primarily due to leaching of toxic chemicals.


[Apropos of possible paired comparison of receptor-binding parameters obtained in one experiment].
The possibility of statistical comparison of receptor-binding parameters obtained on pooled biological material has been analysed. It was concluded that such comparison was possible when the data were processed in Cornish-Bowden plot, even with out repeating analogous experiments. The advantages of this approach over other methods are discussed.


Screening tests for assessing treatability of inorganic industrial wastes by stabilisation/solidification with cement.
Stabilisation/solidification with cementitious or pozzolanic binders (S/S) is an option for reducing leachability of contaminants from residual, predominantly inorganic, industrial wastes and contaminated soils before disposal or reuse. Treatment by S/S is complicated by the fact that the presence of impurities, such as the contaminants and bulk matrix components present in industrial wastes, can have deleterious effects on cements. Therefore, careful laboratory development and testing of S/S formulations are required prior to full-scale application, to avoid technology failures, including problems with handling and contaminant retention. An understanding of cement chemistry and contaminant immobilisation mechanisms has been used to propose a series of test methods and performance thresholds for use in efficient evaluation of the treatability of industrial wastes by S/S, and optimising S/S formulations: measurement of stabilised/solidified product workability, bleeding and setting time (for flowable mixtures) or Proctor compaction (for compactable mixtures), together with unconfined compressive strength, leachability in a batch extraction with distilled water, and hydraulic conductivity.


The effects of dopamine infusion on the postoperative energy expenditure, metabolism, and catecholamine levels of patients after esophagectomy.
Although dopamine is one of the most widely used vasoactive agents, its postoperative thermogenic and metabolic effects have not been studied. In this study, the effects of low-dose dopamine, given at 5 microgram/kg/min, on resting energy expenditure (REE), metabolism, and plasma catecholamine levels were examined in eight postsurgical patients. Dopamine infusion increased REE from 1,839 +/- 171 kcal/day to 2,071 +/- 170 kcal/day, and it decreased to 1,867 +/- 141 kcal/day after cessation of the infusion. Dopamine also increased the plasma levels of glucagon from 109.4 +/- 8.7 pg/ml to 132.5 +/- 8.0 pg/ml, and it decreased to 102.9 +/- 11.1 pg/ml after cessation of the infusion. The plasma levels of dopamine before, during, and after the infusion were 116.1 +/- 18.3, 161.1 +/- 25.6 and 121.4 +/- 17.2 ng/ml, respectively. Insulin and glucose were affected by dopamine, but changes in their plasma levels did not parallel the dopamine levels. Epinephrine and norepinephrine were increased by the infusion of dopamine and continued to increase even after its cessation. The results of this study revealed that low-dose dopamine increased REE in postsurgical patients and that this might be associated with the concomitant increase in plasma glucagon.


A neonate with Coombs-negative hemolytic jaundice with spherocytes but normal erythrocyte indices: a rare case of autosomal-recessive hereditary spherocytosis due to alpha-spectrin deficiency.
The diagnosis of hereditary spherocytosis (HS) in a newborn infant is generally made on the basis of a positive family history, spherocytes on blood film and Coombs-negative hemolytic jaundice of variable severity with an elevated mean corpuscular hemoglobin concentration (MCHC) and a low mean corpuscular volume (MCV). In general, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) quantification of erythrocyte membrane proteins is not needed to make the clinical diagnosis of HS. However, we observed that a neonate with no family history of HS, but with abundant spherocytosis on repeated blood films, Coombs-negative hemolytic jaundice and normal MCHC and MCV measurements, where SDS-PAGE revealed alpha-spectrin deficiency, a rare autosomal-recessive variety of HS that generally has a severe clinical phenotype.


Stable eye versus mouth preference in a live speech-processing task.
Looking at the mouth region is thought to be a useful strategy for speech-perception tasks. The tendency to look at the eyes versus the mouth of another person during speech processing has thus far mainly been studied using screen-based paradigms. In this study, we estimated the eye-mouth-index (EMI) of 38 adult participants in a live setting. Participants were seated across the table from an experimenter, who read sentences out loud for the participant to remember in both a familiar (English) and unfamiliar (Finnish) language. No statistically significant difference in the EMI between the familiar and the unfamiliar languages was observed. Total relative looking time at the mouth also did not predict the number of correctly identified sentences. Instead, we found that the EMI was higher during an instruction phase than during the speech-processing task. Moreover, we observed high intra-individual correlations in the EMI across the languages and different phases of the experiment. We conclude that there are stable individual differences in looking at the eyes versus the mouth of another person. Furthermore, this behavior appears to be flexible and dependent on the requirements of the situation (speech processing or not).


Challenges Facing Women Survivors of Self-Immolation in the Kurdish Regions of Iran: A Qualitative Study.
Women confront many problems after self-immolation, so the purpose of this study was to explore the challenges facing women survivors of self-immolation in the Kurdish Regions of Iran. This study used a qualitative approach and conventional content analysis. Data were collected through semi-structured interviews with 19 Kurdish women who attempted self-immolation in Iran. They were sampled through purposeful sampling and snowball sampling. The Lincoln and Guba criteria were used to strengthen the research. The results of data analysis were categorized into five main categories: 1-psychological problems, 2-lack of social and legal supportive structures, 3-incomplete treatment, 4-poor self-care, and 5-social problems. These categories consist of 19 subcategories. Having been rescued from self-immolation, the women confront many challenges returning to normal life. Reducing these women's problems and paving the way for their return to life requires multi-dimensional and community-based interventions. Therefore, all social organizations and institutes can cooperate and each of them paves part of the way.


Hyperosmolality rapidly reduces atrial-natriuretic-peptide-dependent cyclic guanosine monophosphate production in cultured rat inner medullary collecting duct cells.
The present study was undertaken to explore the acute effect of hyperosmolality on the response of cultured rat inner medullary collecting duct (IMCD) cells to atrial natriuretic peptide (ANP). In contrast to the stimulatory effect of chronic incubation (12 h) in hypertonic medium, it was found that short-term incubation (< 2 h) reversibly suppressed the ANP-dependent cyclic guanosine monophosphate (cGMP) production. Urea, NaCl and mannitol were equi-potent as the osmolyte in suppressing the ANP-dependent cGMP production. Receptor binding assay revealed that hyperosmolality induced a rapid and marked reduction of the maximum binding (Bmax) of ANP without a significant change of the dissociation constant (Kd). Pretreatment with protein kinase C inhibitors (calphostin-C, staurosporin) or with cytoskeleton modulators (cytochalasin-B, colchicine) did not affect the inhibitory effect of hyperosmolality. In conclusion, acute hypertonicity inhibited the ANP-induced cGMP production in contrast to chronic hypertonicity, and reduction of the number of ANP binding sites was considered to be a mechanism responsible for the inhibitory effect of hypertonicity.


Adenocarcinoma with intraductal papillary mucinous neoplasm arising in a duodenal heterotopic pancreas: a case report.
A woman in her 70 s was diagnosed with a tumor in her duodenal wall during a routine visit for diabetes. She subsequently underwent subtotal stomach-preserving pancreatoduodenectomy. Histologically, the tumor was present mainly in the duodenal wall, and atypical cystic ducts were seen in the muscularis propria and subserosa. Invasive well-differentiated adenocarcinoma was seen in the duodenal submucosal and mucosal layers. Heterotopic pancreatic tissue was seen within the tumor, and atypical epithelium had proliferated and replaced the cystic ductal epithelium of the heterotopic pancreas. Therefore, adenocarcinoma with intraductal papillary mucinous neoplasm arising in duodenal heterotopic pancreas was the final histopathological diagnosis, which is considered rare.


Effect of nifedipine on capacitive calcium entry in Jurkat T lymphocytes.
The effect of nifedipine-an antagonist of L-type calcium (Ca(2+)) channels-on capacitative Ca(2+) entry (CCE) was studied in Jurkat T lymphocytes. CCE was induced by a variety of treatments each of which depleted intracellular Ca(2+) stores. Cells were treated with thapsigargin, ionomycin, anti-CD3 antibodies, and phytohaemagglutinin, or pre-incubated in a Ca(2+)-free medium. Activity of CCE was evaluated with a Ca(2+)-free/Ca(2+)-readmission protocol, in Fluo-3 pre-loaded cells. Nifedipine inhibited CCE in a dose-dependent manner. CCE inhibition was not due to non-specific effects on K(+) channels. Nifedipine, did not induce any membrane depolarization, as revealed by measurements of the plasma membrane potential with the fluorescent probe bis-oxonol. Moreover, experiments done under depolarizing conditions (i.e. by substituting Na(+) with K(+) ions in the medium) revealed that nifedipine could inhibit capacitative Ca(2+) entry independently of plasma membrane depolarization. We also demonstrated the presence in our Jurkat T-cells of transcripts for Ca(V)1.3 (alpha(1D)) and Ca(V)1.4 (alpha(1F)) L-type Ca(2+) channels. Verapamil and diltiazem, two unrelated blockers of L-type Ca(2+) channels, were less inhibitory on CCE. Possible mechanisms by which nifedipine interferes with Ca(2+) entry in these cells are discussed.


G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain.
G protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins presumably related in non-canonical Wnt signaling. In this study, we investigated altered GPRC5B expression in the dorsal horn of the spinal cord after spinal nerve injury and its involvement in the development of neuropathic pain. After induction of anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5 spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with silk and cut just distal to the ligature. Seven days after nerve injury, animals were perfused with 4% paraformaldehyde, and the spinal cords were extracted and post-fixed at 4℃ overnight. To identify the expression of GPRC5B and analyze the involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using several markers for neurons and glial cells in spinal cord tissue. After L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the ipsilateral part, as compared to the contralateral part, of the spinal dorsal horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B antibody in the spinal dorsal horn. These results imply that L5 SNL-induced GPRC5B downregulation may affect microglial activation in the spinal dorsal horn and be involved in neuropathic pain.


Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia.
Independent predictors of outcome for ischemic stroke include age and initial stroke severity. Intracranial large-vessel occlusion would be expected to predict poor outcome. Because large-vessel occlusion and stroke severity are likely correlated, it is unclear if largevessel occlusion independently predicts outcome or is simply a marker for stroke severity. A consecutive series of patients with suspected stroke or transient ischemic attack were imaged acutely with computed tomography angiography (CTA). CTAs were reviewed for intracranial large-vessel occlusion as the cause of the stroke. Baseline National Institutes of Health Stroke Scale (NIHSS) score, discharge modified Rankin score, and patient demographics were abstracted from hospital records. Poor neurological outcome was defined as modified Rankin score exceeding 2. Seventy-two consecutive patients with acute ischemic stroke were imaged with CTA. The median (range) time from stroke symptom onset to CT imaging was 183 minutes (25 minutes to 4 days). Median NIHSS score was 6 (1-32) and intracranial large-vessel occlusion was found in 28 (38.9%) patients. Fifty-six percent of patients had a good neurological outcome. In multivariate logistic regression analysis, two variables predicted poor neurological outcome: baseline NIHSS score (OR 1.21, 95% CI [1.07-1.37]) and presence of intracranial large-vessel occlusion (OR 4.48, 95% CI [1.19-16.9]). The predictive value of large-vessel occlusion on outcome was similar to an 8-point increase in NIHSS score. In patients presenting with acute brain ischemia, intracranial large-vessel occlusion independently predicts poor neurological outcome at hospital discharge, as does the presence of a high NIHSS score. Performing routine intracranial vascular imaging on acute stroke patients may allow for more accurate determination of prognosis and may also guide therapy.


Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis.
In this study, we leveraged the combined evidence of rare coding variants and common alleles to identify therapeutic targets for osteoporosis. We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P < 3.6 × 10-7). These genes were highly enriched for a set of known causal genes for osteoporosis (65-fold; P = 2.5 × 10-5). Exome-wide significant genes had 96-fold increased odds of being the top ranked effector gene at a given GWAS locus (P = 1.8 × 10-10). By integrating proteomics Mendelian randomization evidence, we prioritized CD109 (cluster of differentiation 109) as a gene for which heterozygous loss of function is associated with higher bone density. CRISPR-Cas9 editing of CD109 in SaOS-2 osteoblast-like cell lines showed that partial CD109 knockdown led to increased mineralization. This study demonstrates that the convergence of common and rare variants, proteomics and CRISPR can highlight new bone biology to guide therapeutic development.


Impact of maternal dietary exposure to endocrine-acting chemicals on progesterone receptor expression in microdissected hypothalamic medial preoptic areas of rat offspring.
We have previously examined the impact of perinatal exposure to ethinylestradiol (EE), methoxychlor (MXC), diisononyl phthalate (DINP), and genistein (GEN) in maternal diet on rat offspring, and found developmental and/or reproductive toxicity with 0.5 ppm EE, 1200 ppm MXC, and 20,000 ppm DINP. Although the toxicological profile with MXC was similar to the EE case, the population changes in pituitary hormone-producing cells totally differed between the two cases, changes being evident from 240 ppm with MXC. In the present study, to assess the impact of these agents on brain sexual differentiation, region-specific mRNA expression of estrogen receptors (ER) alpha and beta, the progesterone receptor (PR), gonadotrophin-releasing hormone, steroid receptor coactivators (SRC)-1 and -2, and calbindin-D in microdissected hypothalamic medial preoptic areas (MPOAs) at postnatal day 10 was first analyzed in rats exposed to 0.5 ppm-EE from gestational day 15 by real-time RT-PCR. Sexually dimorphic expression of ER alpha and PR was noted with predominance in females and males, respectively, EE up-regulating SRC-1 in males and ER beta and PR in females. Next, we similarly examined expression changes of ER alpha and beta, PR, and SRC-1 in animals exposed to MXC at 24, 240, and 1200 ppm, DINP at 4000 and 20,000 ppm, and GEN at 1000 ppm. MXC at 1200 ppm down- and up-regulated PR in males and females, respectively, and DINP at 20,000 ppm down-regulated PR in females, while GEN did not exert any clear effects. The results thus suggest that agents causing developmental and/or reproductive abnormalities in later life may affect hypothalamic PR expression during the exposure period in early life.


Efficacy and safety of baricitinib and tocilizumab in hospitalized patients with COVID-19: A comparison using systematic review and meta-analysis.
Objective: This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC). Methods: Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363). Results: Treatment with baricitinib [RR, 0.69 (95% CI, 0.50-0.94), p = 0.02, i2 = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71-1.07), p = 0.19, i2 = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, -1.13 days (95% CI, -1.51 to -0.76), p < 0.001, i2 = 0.00%; tocilizumab: mean difference, -2.80 days (95% CI, -4.17 to -1.43), p < 0.001, i2 = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03-1.48), p = 0.02, i2 = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12-1.78), p < 0.001, i2 = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62-0.92), p = 0.01, i2 = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72-1.01), p = 0.07, i2 = 0.00%]. Conclusion: As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.


The crucial role of iron uptake in Aspergillus fumigatus virulence.
Aspergillus fumigatus is an opportunistic fungal pathogen that causes life-threatening infections in immunocompromised individuals. Siderophore-mediated iron acquisition has been shown to be essential for virulence. New studies have revealed that enzymes involved in siderophore biosynthesis and uptake are compartmentalized in peroxisomes and endosome-like vesicles, respectively. Gene and protein expression studies have revealed coordinated regulation of siderophore and sterol metabolism linked to the common precursor mevalonate. Several A. fumigatus transcription factors have been identified that are unexpectedly involved in the regulation of iron homeostasis. New diagnostic and drug treatments are being developed that exploit the requirement of A. fumigatus for extracellular siderophores.


Isolation and characterization of mRNA from Paramecium aurelia.
Total cellular RNA was isolated from the ciliate protozoan Paramecium aurelia by pH 9.5 chloroform/octanol extraction. Passage of this RNA through an oligo(dT)-cellulose column in 0.5 M NaCl resulted in 2--3% binding, indicating the presence of polyadenylic acid sequences. These polyadenylic acid regions were estimated to be 250-500 nucleotides in length, based on their resistance to ribonuclease degradation. The oligo(dT)-cellulose bound RNA sedimented at 14--25 S in sodium dodecyl sulphate/sucrose gradients. The base composition of this RNA is similar to the base composition of the DNA. This RNA was also actively translated into protein by an in vitro protein synthesizing system isolated from wheat germ. Translation was optimal under conditions similar to those used for mammalian mRNA translation. In addition, translation of the P. aurelia oligo(dT)-cellulose bound RNA was inhibited 80% by the analog 7-methylguanosine-5'-phosphate, suggesting the presence of a 5'-capped terminus.


Identification of male-produced aggregation pheromone of the curculionid beetle Sternechus subsignatus.
Analyses of the headspace volatiles produced by males and females of Sternechus subsignatus Boheman (Coleoptera: Curculionidae) revealed seven male-specific compounds. The major component was (E)-2-(3,3-dimethylcyclohexylidene)-ethanol, and the minor components were 1-(2'-hydroxyethyl)-1-methyl-2-isopropenylcyclobutane (grandisol), 7-methyl-3-methyleneoct-6-en-1-ol, (Z)-2-(3,3-dimethylcyclohexylidene)-ethanol, (Z)- and (E)-2-(3,3-dimethylcyclohexylidene)-acetaldehyde, and (E)-2-(3,3-dimethylcyclohexylidene) acetic acid. The latter compound is described for the first time as a natural product. Only four of the seven identified compounds showed electrophysiological activity. Enantioselective gas chromatography showed that the natural grandisol is the (1R,2S)-stereoisomer. The major component, (E)-2-(3,3-dimethylcyclohexylidene)-ethanol, attracted S. subsignatus in olfactometer bioassays. Studies are in progress to evaluate the biological activity of the major component and the EAD-active mixture under field conditions.


A literature review of midtarsal joint function.
This article focuses on nearly 50 years of research by various authors documenting function and motion of the midtarsal joint. Subtalar joint control of the midtarsal joint, axes of motion, and quantification of range of motion are examined. The evolution of the joint from primates to man and the associated changes in functional requirements are considered.


TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.
Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA-the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP-TET interplay. Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.


Current drug use as risk factor for erectile dysfunction: results from an Italian epidemiological study.
Several drugs have been associated with an increased risk of erectile dysfunction (ED). We analysed the role of pharmacological treatments on the risk of ED using data from a cross-sectional study on prevalence and risk factors for ED in the general population in Italy. A total of 2450 men aged more than 18 years were randomly identified by 143 general practioners (GP) among their registered patients and invited to a confidential interview by their GP. Patients were asked 'about their ability to achieve and maintain an erection sufficient for satisfactory sexual performance'. If they were dissatisfied, they were defined as having ED. Out of the 2450 men identified, 440 (18%) refused to participate. The present analysis therefore includes information on 2010 men. After adjustment for related pathologies, anxiolytics and antidepressants showed insignificantly higher odds ratio (ORs, respectively, 1.7 and 2.1); antipsychotic drug use significantly increased the risk of ED (OR 9.0, 95% confidence interval, CI 1.8-44.4). Diuretics (OR 3.1, 95% CI 1.4-6.9) and anticholinergic drugs (OR 12.8, 95% CI 2.7-60.1) were associated with ED risk. No association emerged between ED and H2 antagonists, anticholesterolemic or hypoglycemic drugs. In conclusion, after taking account of related pathologies, our results suggest that men treated with antipsychotic, diuretic and anticholinergic drugs are at greater risk of ED.


Inhibition of acetylcholinesterase by physostigmine analogs: conformational mobility of cysteine loop due to the steric effect of the alkyl chain.
The effect of a series of physostigmine analogs on acetylcholinesterase activity was investigated. The second-order rate constant k(on) of the enzyme-inhibitor complex correlates with the conformational positioning of aromatic residues, especially Trp84, in the transition state complex. The van der Waals interactions are an important structural element of this conformational change. A transient mobility of the cysteine loop (Cys67-Cys94) was confined only to the presence of a significant steric effect. Even with this limitation, however, the steric effect seems to be an appropriate model for future tests on the "back door" hypothesis involving facilitated opening for faster product clearance.


An enzyme immunoassay for the screening of monoclonal antibodies to cyclosporin.
An enzyme-linked immunosorbent assay (ELISA) has been developed which allows hybridoma cell cultures to be tested for the presence of monoclonal antibodies specific for cyclosporin A. Immunization of mice with free cyclosporin was found to be preferable to immunization with cyclosporin-carrier conjugates. It is hoped that the availability of monoclonal antibodies to cyclosporin will clarify the contribution of cyclosporin metabolites to immunosuppression and nephrotoxicity.


Factor Structure, Reliability, and Validity of the Spanish Version of the Children's Florida Obsessive Compulsive Inventory (C-FOCI).
The Children's Florida Obsessive Compulsive Inventory (C-FOCI) is a promising self-report measure of the presence and severity of obsessive-compulsive symptoms in children and adolescents. Although initial research showed it to have adequate psychometric properties, only one study has been published to date, which dealt exclusively with children. The aim of this report was to examine the psychometric properties of the C-FOCI across clinical and community samples of children and adolescents. The sample consisted of 94 Spanish-speaking patients with obsessive-compulsive disorder (OCD) and 1068 healthy community controls, aged 8-19 years. Factor analysis supported two single and independent factors (severity and symptoms), as well as metric invariance across groups for the symptom checklist and the Severity Scale. Results also indicated good reliability in terms of internal consistency and temporal stability, significant and high correlations with other OCD measures, and acceptable sensitivity and specificity for detect OCD. In summary, the C-FOCI is a promising, brief measure of 22 items for screening OCD symptoms and severity in children and adolescents.


[Anticoagulation].
Anticoagulant drugs belong to the group of antithrombotic agents and are successfully used in the prophylaxis and treatment of thromboembolic disorders. The use of anticoagulants in the prevention of deep venous thrombosis has significantly lowered the risk of venous thrombosis and fatal pulmonary embolisms even in high-risk situations such as orthopedic surgery. Anticoagulants play a central role in the treatment of acute venous thrombosis and in the prevention of recurrent events. Long-term anticoagulation therapy with orally active anticoagulants significantly reduces the risk of thromboembolic complications in patients showing cardiac arrhythmias. Whereas a few years ago heparins and vitamin K antagonists were the dominant anticoagulants, today a wide range of anticoagulants with improved pharmacological profiles are available. It remains an open question whether these new anticoagulants will improve the efficacy, safety, and acceptance of anticoagulant treatment approaches.


[Non-neurological overactive bladder and pelvic-perineal pathology in women].
The aim was to synthesize current knowledge on overactive bladder (OAB) and female pelvic-perineal diseases. A systematic literature review based on PubMed, Embase and Google Scholar was conducted in April 2020. Women with pelvic organ prolapse very often have OAB. Prolapse surgery should be considered if the prolapse is symptomatic and never be indicated in case of overactive bladder symptoms solely. In case of symptomatic prolapse and OAB, pessary and surgical treatments are effective on both pathologies up to 71 % of the cases. OAB may occur in parallel or as part of a menopausal genitourinary syndrome. In the latter case, only local estrogen therapy is effective. OAB may occur alongside stress urinary incontinence (SUI) or be integrated into mixed urinary incontinence. The initial treatment should be based on the most troublesome symptoms. In case of SUI, the outcome of surgical treatment on OAB remains uncertain. De novo, OAB follows prolapse or SUI surgery. It requires investigations to exclude urinary tract infection, bladder outlet obstruction or erosion. The treatment is the same as OAB. The clinician's challenge is to draw a balance between the OAB and a pelvic-perineal pathology in order to adapt the treatment.


Crosstalk between Sertoli and Germ Cells in Male Fertility.
Spermatogenesis is supported by intricate crosstalk between Sertoli cells and germ cells including spermatogonia, spermatocytes, haploid spermatids, and spermatozoa, which takes place in the epithelium of seminiferous tubules. Sertoli cells, also known as 'mother' or 'nurse' cells, provide nutrients, paracrine factors, cytokines, and other biomolecules to support germ cell development. Sertoli cells facilitate the generation of several biologically active peptides, which include F5-, noncollagenous 1 (NC1)-, and laminin globular (LG)3/4/5-peptide, to modulate cellular events across the epithelium. Here, we critically evaluate the involvement of these peptides in facilitating crosstalk between Sertoli and germ cells to support spermatogenesis and thus fertility. Modulating or mimicking the activity of F5-, NC1-, and LG3/4/5-peptide could be used to enhance the transport across the blood-testis barrier (BTB) of contraceptive drugs or to treat male infertility.


A standardized implementation of multicenter quality improvement program of very low birth weight newborns could significantly reduce admission hypothermia and improve outcomes.
Admission hypothermia (AH, < 36.5℃) remains a major challenge for global neonatal survival, especially in developing countries. Baseline research shows nearly 89.3% of very low birth weight (VLBW, < 1500 g) infants suffer from AH in China. Therefore, a prospective multicentric quality improvement (QI) initiative to reduce regional AH and improve outcomes among VLBW neonates was implemented. The study used a sequential Plan-Do-Study-Act (PDSA) approach. Clinical data were collected prospectively from 5 NICUs within the Sino-Northern Neonatal Network (SNN) in China. The hypothermia prevention bundle came into practice on January 1, 2019. The clinical characteristics and outcomes data in the pre-QI phase (January 1, 2018- December 31, 2018) were compared with that from the post-QI phase (January 1, 2019-December 31, 2020). Clinical characteristics and outcomes data were analyzed. A total of 750 in-born VLBW infants were enrolled in the study, 270 in the pre-QI period and 480 in the post- QI period, respectively. There were no significant differences in clinical characteristics of infants between these two phases. Compared with pre-QI period, the incidence of AH was decreased significantly after the QI initiative implementation in the post-QI period (95.9% vs. 71.3%, P < 0.01). Incidence of admission moderate-to-severe hypothermia (AMSH, < 36℃) also decreased significantly, manifesting a reduction to 38.5% in the post-QI (68.5% vs 30%, P < 0.01). Average admission temperature improved from after QI (35.5 [Formula: see text] 0.7℃ vs. 36.0 [Formula: see text] 0.6℃, P < 0.01). There was no increase in proportion the number of infants with a temperature of > 37.5 °C or thermal burns between the two groups. The risk ratio of mortality in infants during the post-QI period was significantly lower in the post-QI period as compared to the pre-QI period [adjusted risk ratio (aRR): 0.26, 95% confidence interval (CI): 0.13-0.50]. The risk ratio of late-onset neonatal sepsis (LOS) also significantly lowered in the post-QI period (aRR: 0.66, 95% CI: 0.50-0.87). Implementation of multicentric thermoregulatory QI resulted in a significant reduction in AH and AMSH in VLBW neonates with associated reduction in mortality. We gained a lot from the QI, and successfully aroused the attention of perinatal medical staff to neonatal AH. This provided a premise for continuous quality improvement of AH in the future, and might provide a reference for implementation of similar interventions in developing countries. Trial registration number: ChiCTR1900020861 . Date of registration: 21 January 2019(21/01/2019). Prospectively registered.


Pediatric spinal sonography. Part I: Anatomy and examination technique.
Ultrasonography with high resolution technique enables the differentiation of intra- and paraspinal structures in a significant way. Conditions, examination technique, and sonographic anatomy of the os sacrum, the lumbar and dorsal spinal canal as well as the cranio-cervical junction are presented.


Rescue of Mdm4-deficient mice by Mdm2 reveals functional overlap of Mdm2 and Mdm4 in development.
The Mdm2 and Mdm4 genes are amplified and overexpressed in a variety of human cancers and encode structurally related oncoproteins that bind to the p53 tumor suppressor protein and inhibit p53 activity. Mice deleted for either Mdm2 or Mdm4 die during embryogenesis, and the developmental lethality of either mouse model can be rescued by concomitant deletion of p53. However, the phenotypes of Mdm2 and Mdm4-deficient mice suggest that Mdm2 and Mdm4 play nonoverlapping roles in regulating p53 activity during development, with Mdm2 regulating p53-mediated cell death and Mdm4 regulating p53-mediated inhibition of cell growth. Here, we describe complete rescue of Mdm4-deficient mice by expression of an Mdm2 transgene, and demonstrate that Mdm2 can regulate both p53-mediated apoptosis and inhibition of cell growth in the absence of Mdm4 in primary cells. Furthermore, deletion of Mdm4 enhances the ability of Mdm2 to promote cell growth and tumor formation, indicating that Mdm4 has antioncogenic properties when Mdm2 is overexpressed.


Intrinsic asthma and bacterial histamine release via lectin effect.
Bacteria-induced histamine release from basophil leukocytes was observed in vitro in both children with intrinsic asthma (IA) as well as in normal individuals. In vivo the release is suggested to take place only in the lung of IA patients, where a defective pulmonary barrier would permit the bacteria to enter, but not in healthy individuals. The study indicates that two different mechanisms of bacterial histamine release might exist, an IgE-mediated reaction and a non-immunological mechanism consisting of a direct interaction with the basophil cell surface. The non-allergic mechanism might depend on a lectin effect where bacterial surface lectins interact with the basophil cell surface leading to release of histamine. Inhibition studies with carbohydrates suggest a multi-lectin reaction in the bacterial histamine release involving several types of lectins on the bacterial membrane reacting with different carbohydrate moieties on the cell surface of basophil leukocytes.


On-line monitoring of yeast cell growth by impedance spectroscopy.
The application of impedance spectroscopy to estimate on-line cell concentration was studied. The estimation was based on the relative variation between electrical impedance measured at low (10 kHz) and high frequencies (10 MHz). Studies were carried out to characterise the influence of changes in physical and chemical parameters on the impedance measurement. Two different possibilities to perform on-line measurements were tested: a simple set-up, based on an in situ probe, gave good results but was not suitable for high agitation and aeration rates. An ex situ flow-through on-line measuring cell was used to overcome these problems, showing a better performance. The use of this set-up for the growth monitorisation of a Saccharomyces cerevisiae culture showed an efficient performance, having the correlation between estimated and measured S. cerevisiae a Pearson coefficient of 0.999.


Volvulus of the cecum. Report of 26 cases and review of the literature.
The management of cecal volvulus is controversial. From 1971 to 1986, 26 patients with cecal volvulus were treated at Malmö General Hospital. Treatment and patient follow-up are presented, together with a review of 350 patients reported in the literature during the past 15 years. Anatomic background and types of volvulus are described. Simple detorsion is an alternative in high-risk patients without gangrene, but resection is the method of choice also when there is no gangrene present.


A literature review of leadership training and a novel conceptual model of leader-member exchange theory for new dentists.
The purpose of the paper is to describe the current state of leadership and leader-member exchange (LMX) theory in dentistry and develop a novel conceptual model of LMX to guide future research and highlight the importance of enhancing leadership training for new dentists. A literature review exploring leadership in dentistry and LMX in dentistry was completed. The findings were analyzed with framework analysis to develop a novel conceptual model of LMX specific to dentistry. LMX theory was applied to leadership in dentistry, including a focus on new dentists, senior dentists, other dental team members and the patient. A new conceptual model of the New Dentist LMX Quartet, which is unique and specific to new dentist teams, was developed. The study identifies the need for research in LMX in dentistry, contributes a new conceptual model for LMX theory and identifies future research. Practitioners, policymakers and educators can utilize this information to explore concepts in leadership and improve training and dental practice. No other studies specifically exploring LMX in dentistry for new dentists exist. The current literature review and conceptual paper begins the conversation on developing understanding of leadership in dentistry through further research.


[Progress in researches on the relation between chronic prostatitis and cytokines].
Chronic prostatitis is a common andrologic disease. The etiology and pathogensis of the disease are not yet completely understood. This article reviews the origin and the molecular strucure of cytokines and their role in the pathogenesis of prostatitis, especially chronic nonbacterial prostatitis/chronic pelvic pain syndrome.


Social Inequalities on Selected Determinants of Active Aging and Health Status Indicators in a Large Brazilian City (2003-2010).
To assess trends in social inequalities among 2,624 elderly living in Belo Horizonte, Brazil, in three domains of the World Health Organization's Active Aging model (physical environment, social determinants, use of health services) and health status indicators. Data came from two representative household surveys conducted in 2003 and 2010. Social inequality was measured by the slope and the relative index of inequality. Educational level was used to define socioeconomic status. Significant improvements were observed in the prevalence rates of 7 out of 12 indicators. However, the social inequalities persisted through 10 out of 12 selected active aging and health status indicators, except for fear of falling on the sidewalks/crossing the streets and fear of being robbed. Social inequalities persistence might be assigned to the continuity of unequal distribution of resources among groups with different educational levels.


Tumor necrosis factor alpha (TNF) suppresses cAMP response element (CRE) activity and nuclear CRE binding protein in MA-10 mouse Leydig tumor cells.
TNF is known to suppress gonadotropin-induced steroid secretion by Leydig cells. However, the mechanisms by which this occurs are largely unknown. Because expression of many steroidogenic proteins is regulated by the PKA pathway, effects of TNF on CRE activity were examined using MA-10 mouse Leydig tumor cells. The cells were transfected with a CRE-luciferase construct, and stimulated with either LH or 8Br-cAMP in the presence or absence of TNF. TNF suppressed, LH-stimulated and 8Br-cAMP stimulated CRE activity. TNF also suppressed CRE activity stimulated with a PKA expression vector. Further experiments suggested that the effect of TNF on CRE activity was not mediated by the NF-kappaB pathway. TNF did not affect levels of either CREB or phospho-CREB in whole cell lysates; however, TNF decreased both CREB and phospho-CREB in nuclear extracts in a time-dependent manner. The decrease in nuclear CREB is likely to be a major mechanism of the suppressive effects of TNF on steroidogenesis in MA-10 Leydig cells.


Vascular thrombosis induced by direct electric current. A new technique for therapeutic embolisation; animal experimentation; first clinical applications.
A first series of experiments showed that the passage of a direct current along a positive electrode immersed in heparinised blood caused the formation of an adhering clot whose diameter increased with time and current intensity. A second series of experiments was done on 10 rabbits as follows: under general anaesthesia, a catheter used as a guide to the positive electrode was surgically inserted in the abdominal aorta. The negative electrode was placed on the thigh. A direct current (10 mA, 10V) was applied for 10-20 min. The first two clinical applications in man of this new method of treatment by electric current thrombosis were carried out using catheterisation of branches of the external carotid and cervical arteries.


Synthesis of barbiturate-based methionine aminopeptidase-1 inhibitors.
The syntheses of a new class of barbiturate-based inhibitors for human and Escherichia Coli methionine aminopeptidase-1 (MetAP-1) are described. Some of the synthesized inhibitors show selective inhibition of the human enzyme with high potency.


Antidiabetic and antioxidant functionality associated with phenolic constituents from fruit parts of indigenous black jamun (Syzygium cumini L.) landraces.
Fruit phenolics are important dietary antioxidant and antidiabetic constituents. The fruit parts (pulp, seed, seed coat, kernel) of underutilized indigenous six black jamun landraces (Syzygium cumini L.), found in Gir forest region of India and differed in their fruit size, shape and weight, are evaluated and correlated with antidiabetic, DPPH radical scavenging and phenolic constituents. The α-amylase inhibitors propose an efficient antidiabetic strategy and the levels of postprandial hyperglycemia were lowered by restraining starch breakdown. The sequential solvent systems with ascending polarity-petroleum ether, ethyl acetate, methanol and water were performed for soxhlet extraction by hot percolation method and extractive yield was found maximum with methanolic fruit part extracts of six landraces. The methanolic extracts of fruit parts also evidenced higher antidiabetic activity and hence utilized for further characterization. Among the six landraces, pulp and kernel of BJLR-6 (very small, oblong fruits) evidenced maximum 53.8 and 98.2% inhibition of α-amylase activity, respectively. The seed attained inhibitory activity mostly contributed by the kernel fraction. The inhibition of DPPH radical scavenging activity was positively correlated with phenol constituents. An HPLC-PDA technique was used to quantify the seven individual phenolics. The seed and kernel of BJLR-6 exhibited higher individual phenolics-gallic, catechin, ellagic, ferulic acids and quercetin, whereas pulp evidenced higher with gallic acid and catechin as α-amylase inhibitors. The IC50 value indicates concentration of fruit extracts exhibiting ≥50% inhibition on porcine pancreatic α-amylase (PPA) activity. The kernel fraction of BJLR6 evidenced lowest (8.3 µg ml-1) IC50 value followed by seed (12.9 µg ml-1), seed coat (50.8 µg ml-1) and pulp (270 µg ml-1). The seed and kernel of BJLR-6 inhibited PPA at much lower concentrations than standard acarbose (24.7 µg ml-1) considering good candidates for antidiabetic herbal formulations.


Effects of colonic electrical stimulation using different individual parameter patterns and stimulation sites on gastrointestinal transit time, defecation, and food intake.
This study aimed to compare the effects of colonic electrical stimulation (CES) on gastrointestinal transit time (GITT), energy consumption, stool frequency, stool consistency, and food intake using different individual parameter patterns and stimulation sites. Eight beagle dogs underwent surgery and CES. First, CES was conducted to determine the individual parameters with different pulse configurations, based on symptoms. Second, influences on energy consumption and GITT were compared between CES sessions with different pulse configurations. Third, GITT, stool frequency, stool consistency, and food intake were compared to assess the effects of CES at different stimulation sites. The individual parameters varied greatly among the dogs. In proximal colon electrical stimulation (PCES) and rectosigmoid colon electrical stimulation (RCES), energy consumption was lower with the constant pulse width mode than with the constant pulse amplitude mode (p = 0.012 and p = 0.018, respectively). There was no statistical difference between the two pulse configurations in GITT assessment. The PCES, RCES, and sequential CES sessions significantly accelerated GITT compared to sham stimulation. There was no statistical difference in GITT between PCES, RCES, and sequential CES sessions. Compared to sham CES session, RCES and sequential CES sessions exhibited significant higher stool frequency (p < 0.001 and p = 0.001, respectively), and PCES and RCES sessions inhibited food intake (p = 0.003 and p = 0.002, respectively). Constant pulse width mode is an appropriate pulse configuration for individual CES. At different stimulation sites, CES may exert different effects on stool frequency and food intake. This study provides an experimental basis for the clinical application of CES.


Use of the 3-vessel view to record Doppler velocity waveforms from the aortic isthmus in normally grown and growth-restricted fetuses: comparison with the long aortic arch view.
Aortic isthmus (AoI) velocity waveforms are considered powerful indicators of hemodynamic deterioration in intrauterine growth-restricted (IUGR) fetuses. However, technical difficulties in sampling AoI velocity waveforms from the longitudinal aortic arch (LAA) have limited its clinical application thus far. In this study, we tested the possibility of recording AoI velocity waveforms from the 3-vessel (3V) view of the fetal mediastinum and comparing the agreement of these measurements with recordings from the LAA. Doppler measurements of the pulsatility index (PI) from the AoI were performed in 70 fetuses (20 IUGR and 50 normally grown) between 20 and 34 weeks' gestation. All measurements were sampled in both the LAA and 3V views by the same investigator. Reliability was evaluated with intraclass correlation coefficients (ICCs), and Bland-Altman plots were generated. The time required to complete the measurements was compared. A high degree of reliability was observed between PI values obtained from LAA and 3V views in both IUGR and normally grown fetuses (all fetuses: ICC, 0.976; 95% confidence interval [CI], 0.961-0.985; normally grown: ICC, 0.839; 95% CI, 0.731-0.906; IUGR: ICC, 0.954; 95% CI, 0.886-0.982). However, recordings from the 3V view were significantly less time-consuming than those from the LLA view (mean +/- SD, 30.4 +/- 14.2 versus 52.8 +/- 29.4 seconds; P < .0001) and showed higher intraobserver reproducibility. In IUGR and normally grown fetuses, AoI waveforms can be reliably obtained from the 3V view with higher reproducibility and a shorter recording time.


The development of serum immunoglobulins G, A and M in Australian Aboriginal infants.
Serum levels of immunoglobulins G, A and M (IgG, IgA and IgM) were studied in a population of Aboriginal infants from birth to 2 1/2 years of age. Serum levels of all three immunoglobulins were found to be consistently higher than in studies of white children. This is attributed to increased exposure of Aboriginal infants to infectious agents from early in life.


Enzymatic formation and chemical synthesis of an active metabolite of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent regulator of cholesterol metabolism.
The enzymatic (rat liver mitochondria) conversion of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one to 5 alpha-cholest-8(14)-ene-3 beta,26-diol-15-one is described. The enzymatic product was judged, on the basis of IH and 13C NMR studies, to be a 4:1 mixture of its 25R and 25S isomers. (25R)-5 alpha-Cholest-8(14)-ene-3 beta,26-diol-15-one was prepared through a five-step synthesis from (25R)-26-hydroxycholesterol. The (25R) isomer of the new compound was found to be highly active in the suppression of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells and to inhibit the esterification of cholesterol in jejunal microsomes.