Discovery of Key Dioxygenases that Diverged the Paraherquonin and Acetoxydehydroaustin Pathways in Penicillium brasilianum.
Paraherquonin (1), a fungal meroterpenoid produced by Penicillium brasilianum NBRC 6234, possesses a unique, highly congested hexacyclic molecular architecture. Here we identified the biosynthetic gene cluster of 1 (the prh cluster) and elucidated the pathway up to berkeleydione (2), which serves as the key intermediate for the biosynthesis of 1 as well as many other meroterpenoids. Interestingly, the nonheme iron and α-ketoglutarate-dependent dioxygenase PrhA constructs the cycloheptadiene moiety to afford 2 from preaustinoid A1 (6), probably via the homoallyl-homoallyl radical rearrangement. Additionally, another fungal strain, P. brasilianum MG11, which produces acetoxydehydroaustin instead of 1, was found to have a gene cluster nearly identical to the prh cluster. The dioxygenase encoded by the cluster shares 92% sequence identity with PrhA, and also accepts 6 but produces preaustinoid A3 (17) with a spiro-lactone system, generating a diverging point for the two different meroterpenoid pathways in the same species.


An evaluation of meropenem/vaborbactam for the treatment of nosocomial pneumonia.
Introduction: Nosocomial pneumonias are the second most common healthcare-associated infections (HCAIs), often associated with the presence of Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter species, and Enterobacter species. Increasing use of carbapenems has led to an increase in the prevalence of carbapenem-resistant gram-negative organisms, such as carbapenem-resistant Enterobacterales (CRE), P. aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), limiting treatment options for patients at high-risk of multi-drug resistant (MDR) gram-negative pathogens. Areas covered: The purpose of this review is to discuss the role of meropenem/vaborbactam, a beta-lactam combined with a novel non-beta-lactam cyclic boronic acid beta-lactamase inhibitor (BLI), for the treatment of nosocomial pneumonia based on its chemistry, pharmacokinetics/dynamics, microbiological spectrum of activity, mechanisms of resistance, safety, and clinical efficacy. Expert opinion: Currently, any utilization of meropenem/vaborbactam beyond its FDA-approved indication for complicated urinary tract infections is considered off-label use; however, based on the pulmonary penetration of meropenem/vaborbactam, it is highly likely to be a safe and effective alternative to more toxic agents, like aminoglycosides and polymixins, for targeted therapy in pulmonary infections due to CRE. Unfortunately, the multifactorial resistance pattern of CRPA and other non-lactose-fermenting gram-negative bacteria restricts activity against these organisms which are common pathogens implicated in nosocomial pneumonia.


Two Feedback-Insensitive Enzymes of the Aspartate Pathway in Nicotiana sylvestris.
Lysine and threonine overproducer mutants in Nicotiana sylvestris, characterized by an altered regulation of, respectively, dihydrodipicolinate synthase and aspartate kinase activities, were crossed to assess the effects of the simultaneous presence of these genes on the biosynthesis of aspartate-derived amino acids. The monogenic dominant behavior of both resistance traits was confirmed, and their loci were found to be unlinked. Study of the inhibition properties of dihydrodipicolinate synthase and aspartate kinase activities in RAEC-1 x RLT 70 confirmed the heterozygote state of both mutations, because only half of their lysine-sensitive activity could still be inhibited by this negative effector. Analysis of the free amino acid pool during the growth of the double mutant revealed a major free lysine overproduction reaching up to 50% of the total pool, whereas the other aspartate-derived amino acids remained equally or even less abundant than in the wild type. An abnormal phenotype was clearly associated with such high levels of lysine accumulation, which points out the possible role of this amino acid in the developmental features of the plant. Comparison of the amino acid content, free and total (free + protein-bound), between the wild type, the two mutants, and the double mutant obtained by crossing them brings new insights on the regulation of the aspartate pathway, and on its implications in relationship to plant nutritional value improvement.


Muscle morphological and strength adaptations to endurance vs. resistance training.
Fascicle angle (FA) is suggested to increase as a result of fiber hypertrophy and furthermore to serve as the explanatory link in the discrepancy in the relative adaptations in the anatomical cross-sectional area (CSA) and fiber CSA after resistance training (RT). In contrast to RT, the effects of endurance training on FA are unclear. The purpose of this study was therefore to investigate and compare the longitudinal effects of either progressive endurance training (END, n = 7) or RT (n = 7) in young untrained men on FA, anatomical CSA, and fiber CSA. Muscle morphological measures included the assessment of vastus lateralis FA obtained by ultrasonography and anatomical CSA by magnetic resonance imaging of the thigh and fiber CSA deduced from histochemical analyses of biopsy samples from m. vastus lateralis. Functional performance measures included VO2max and maximal voluntary contraction (MVC). The RT produced increases in FA by 23 ± 8% (p < 0.01), anatomical CSA of the knee extensor muscles by 9 ± 3% (p = 0.001), and fiber CSA by 19 ± 7% (p < 0.05). RT increased knee extensor MVC by 20 ± 5% (p < 0.001). END increased VO2max by 10 ± 2% but did not evoke changes in FA, anatomical CSA, or in fiber CSA. In conclusion, the morphological changes induced by 10 weeks of RT support that FA does indeed serve as the explanatory link in the observed discrepancy between the changes in anatomical and fiber CSA. Contrarily, 10 weeks of endurance training did not induce changes in FA, but the lack of morphological changes from END indirectly support the fact that fiber hypertrophy and FA are interrelated.


Synthesis of new naphtho[2,3-f]quinoxaline-2,7,12(1H)-trione and anthra-9,10-quinone dyes from furan-2,3-diones.
Novel naphtho[2,3-f]quinoxaline-2,7,12(1H)-trione and anthra-9,10-quinone dyes were synthesized in good yield from furan-2,3-diones using 1,2-diaminoanthra-9,10-quinone and 1,4-diaminoanthra-9,10-quinone. The chromophores were characterized by molecular spectroscopy methods.


Predictive value of (99m)Tc-HMPAO-SPECT for neurological Outcome/Recovery at the acute stage of stroke.
Combined perfusion and oxygen metabolism PET imaging is highly predictive of spontaneous outcome after middle cerebral artery (MCA) stroke, independent of clinical scores, but whether the assessment of perfusion alone by SPECT provides similar information remains unclear. We have assessed the prognostic value of (99m)Tc-HMPAO-SPECT at the acute stage of stroke. Twenty-seven first-ever nonhemorrhagic MCA territory stroke patients were prospectively studied 4-20 h (mean: 12 h) after onset with (99m)Tc-HMPAO-SPECT. None was part of a therapeutic trial or received thrombolysis. Neurological deficits were quantified at admission and 2 months later with Orgogozo's MCA scale. SPECT images were visually classified by 3 independent observers into one of three patterns, as follows: pattern I = marked and extensive tracer hypofixation; pattern II = moderate and/or focal hypofixation with or without combined hyperfixation, and pattern III = normal or increased uptake without hypofixation. In addition to this visual analysis, we also calculated a voxel-based 'hypoperfusion score', an index of severity x extent of hypofixation according to Mountz's method. There was a good intra- and interobserver agreement. After consensus, 9, 14 and 4 patients were classified in patterns I, II and III, respectively. These patterns had a significant predictive value for raw outcome but not for percentage recovery (p = 0.008 and p = 0.127, respectively). Thus, all patients in pattern III had a good outcome, while most (but not all) patients in pattern I had a poor or intermediate outcome; pattern II patients were more evenly distributed among outcomes. Hypoperfusion scores were highly significantly positively correlated with both 2-month outcomes and percentage recoveries, even after controlling the predictive value of day 0 MCA scores by partial correlations. We found that SPECT had a significant added predictive value even when compared to admission neurological scores. Although less accurate than PET, (99m)Tc-HMPAO-SPECT may help to predict spontaneous individual neurological evolution, especially whenever perfusion images are normal or show an increased tracer uptake without associated hypofixation.


PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update.
Studies performed in the past years showed PTNP22 1858 C > T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858 C > T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858 C > T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR = 1.54, 95% confidence interval (CI) = 1.38-1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR = 2.04, 95% CI = 1.09-3.82, p value = .030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR = 0.62, 95% CI = 0.54-0.72, p value = .000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR = 1.47, p value = .000) and Latin (OR = 2.41, p value = .000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR= 1.31; p value = .54) and African (OR = 2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858 C > T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858 C > T as a potential genetic marker in SLE susceptibility.


Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis.
(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients—32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0−0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine.


Role of mucosal inflammation in eosinophilic esophagitis: review of the literature.
Eosinophilic esophagitis (EE) is increasingly recognized in adults. It is an inflammatory disease of the esophageal mucosa, with variable presentation, unresponsive to acid suppression therapy. The diagnosis requires histological confirmation of intense eosinophilic infiltration on esophageal biopsy specimen, however exact criteria required to make a diagnosis of EE is still being debated and a clear differentiation from gastroesophageal reflux disease (GERD) is important. Allergen elimination or anti-inflammatory therapy may be effective in such patients. The imperfect diagnostic criteria for EE mandate an understanding of the immunology and the pathophysiology of the disease. It may facilitate the introduction of novel treatment modalities in an individual unresponsive to acid suppression therapy. This paper describes basic elements of the immune-mediated injury to the esophageal mucosa and management aspects to provide a better understanding of the condition.


A parallel distributed processing model of stimulus-stimulus and stimulus-response compatibility.
A parallel distributed processing (PDP) model is proposed to account for choice reaction time (RT) performance in diverse cognitive and perceptual tasks such as the Stroop task, the Simon task, the Eriksen flanker task, and the stimulus-response compatibility task that are interrelated in terms of stimulus-stimulus and stimulus-response overlap (Kornblum, 1992). In multilayered (input-intermediate-output) networks, neuron-like nodes that represent stimulus and response features are grouped into mutually inhibitory modules that represent stimulus and response dimensions. The stimulus-stimulus overlap is implemented by a convergence of two input modules onto a common intermediate module, and the stimulus-response overlap by direct pathways representing automatic priming of outputs. Mean RTs are simulated in various simple tasks and, furthermore, predictions are generated for complex tasks based on performance in simpler tasks. The match between simulated and experimental results lends strong support for our PDP model of compatibility.


Revisional surgery after laparoscopic sleeve gastrectomy.
The recent increase in the frequency of bariatric surgery, especially laparoscopic sleeve gastrectomy, is associated with an increase in the frequency of revisional bariatric surgery. The causes of this are numerous but can be summarized as: (1) late fistulae (2) stenosis; (3) gastroesophageal reflux; and (4) weight regain (by increasing or not increasing the gastric volume). We present below a review of the clinical features, diagnosis, and treatment of them.


Endometriosis fertility index predicts pregnancy in women operated on for moderate and severe symptomatic endometriosis.
Endometriosis Fertility Index (EFI) is a clinical staging system created to predict spontaneous pregnancy outcomes in patients with endometriosis. The present study aimed at evaluating the performance of EFI in symptomatic patients, submitted to laparoscopy for moderate and severe endometriosis associated to infertility in a Brazilian population. Seventy-seven women with endometriosis and pelvic pain, who desired to become pregnant, were selected from a tertiary care unit between those operated on between May 2007 and March 2017. All of them were submitted to laparoscopy for the surgical treatment of endometriosis and allowed to attempt natural conception for 36 months or immediately referred to in vitro fertilization (IVF). EFI was calculated according to surgical description and clinical information in medical records. Pregnancy rates and live birth rates after natural conception or IVF are reported and correlated to EFI. Fifty-three women tried natural conception and 24 were referred to IVF. Of the 53 who tried natural conception, 29 achieved pregnancy (54.7%) and 28 had live birth (52.8%). The majority of pregnancies (82.7%) occurred in the first 12 months after surgery and 75% of the patients who became spontaneously pregnant had EFI ≥ 7. Of the 24 patients referred to IVF, 13 became pregnant (54.1%) and 10 had live birth (41.7%). Infertility duration of 36 months or more and the presence of endometrioma increased the probability of having EFI ≤ 5. The overall live birth rate (LBR) for patients with low EFI scores (2-4) was 17% compared with 83.8% for those with higher EFI scores (6-9). EFI predicts pregnancy rates in patients operated on for moderate and severe endometriosis. Scores seem also to predict pregnancy rates after IVF.


Impact of urodynamic studies on the surgical management of spinal cord tethering.
To determine the usefulness of urodynamic studies in the management of children with a suspected tethered spinal cord, the authors retrospectively reviewed case records of 25 patients evaluated both pre- and postoperatively using this diagnostic adjunct. All patients were also evaluated with magnetic resonance imaging or computerized tomography myelography. Seven patients who presented initially with orthopedic deformity, skin stigmata, and neurological problems underwent primary cord untethering (Group 1). All seven patients were urologically asymptomatic; all but one had normal findings on urodynamic study. Eighteen patients with prior myelomeningocele closure underwent secondary untethering (Group 2). They presented with urological (11 cases), neurological (three cases), or both urological and neurological (four cases) deterioration. All patients underwent surgery via a microsurgical technique. At a mean follow-up time of 2 years, the only Group 1 patient with preoperative abnormal urodynamic findings normalized following untethering, whereas another asymptomatic patient showed worsened results on his postoperative study. In Group 2, all seven patients with preoperative neurological deterioration improved. Ten of the 15 patients who had isolated or associated preoperative clinical urological deterioration improved or stabilized, whereas five displayed continued deterioration in their bladder function. With respect to urodynamic studies, there was a significant increase in total and pressure-specific bladder capacities following untethering. We conclude that urodynamic studies are useful both diagnostically and in follow-up examinations of patients with tethered cord, that disturbances identified by these studies often precede clinical manifestations of deterioration, and that spinal cord untethering favorably influences the urological status in most patients.


The poplar glycosyltransferase GT47C is functionally conserved with Arabidopsis Fragile fiber8.
Xylan is the major hemicellulose in dicot wood. Unraveling genes involved in the biosynthesis of xylan will be of importance in understanding the process of wood formation. In this report, we investigated the possible role of poplar GT47C, a glycosyltransferase belonging to family GT47, in the biosynthesis of xylan. PoGT47C from the hybrid poplar Populus alba x tremula exhibits 84% sequence similarity to Fragile fiber8 (FRA8), which is involved in the biosynthesis of glucuronoxylan in Arabidopsis. Phylogenetic analysis of glycosyltransferase family GT47 in the Populus trichocarpa genome revealed that GT47C is the only close homolog of FRA8. In situ hybridization showed that the PoGT47C gene was expressed in developing primary xylem, secondary xylem and phloem fibers of stems, and in developing secondary xylem of roots. Sequence analysis suggests that PoGT47C is a type II membrane protein, and study of the subcellular localization demonstrated that fluorescent protein-tagged PoGT47C was located in the Golgi. Immunolocalization with a xylan monoclonal antibody LM10 revealed a nearly complete loss of xylan signals in the secondary walls of fibers and vessels in the Arabidopsis fra8 mutant. Expression of PoGT47C in the fra8 mutant restored the secondary wall thickness and xylan content to the wild-type level. Together, these results suggest that PoGT47C is functionally conserved with FRA8 and it is probably involved in xylan synthesis during wood formation.


Discontinuation of respiratory isolation for possible tuberculosis: do two negative sputum smear results suffice?
Analysis of acid-fast bacillus smear results at a hospital with a moderate incidence of tuberculosis confirms recent recommendations that 2 negative smear results suffice for discontinuation of respiratory isolation. Use of polymerase chain reaction analysis further increases the confidence with which the diagnosis of active tuberculosis likely to be transmitted to others can be excluded.


Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma.
The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma. A large, multicenter case-control study of Caucasian and African-American women who were diagnosed at age < 65 years with their first invasive breast tumor from July 1, 1994 through April 30, 1998 was conducted. In-person interviews were conducted with 1749 postmenopausal patients, and their responses were compared with the responses of 1953 postmenopausal control women identified through random-digit dialing who met the study criteria of being postmenopausal at the time of diagnosis. Polytomous logistic regression was used to calculate the odds ratio (OR) as an estimate of the relative risk and to compute the 95% confidence interval (95%CI) associated with the use of various regimens of hormone replacement therapy (HRT) among women diagnosed with ductal breast carcinoma, lobular (or mixed lobular and ductal) breast carcinoma, and a grouping of other histologic types of breast carcinoma. Ever use of unopposed estrogen therapy (ERT) was not associated with an increase in the risk of any histologic type of breast carcinoma. The risk of invasive lobular breast carcinoma and the risk of breast carcinoma of the grouping of other histologies increased among women currently using CHRT (OR, 2.2; 95%CI, 1.4-3.3; and OR, 1.9; 95%CI, 1.0-3.4, respectively). The risk increase was greater for the mixed lobular-ductal type than for the pure lobular type of breast carcinoma, although the difference was not statistically significant. There was some indication that >or= 5 years of continuous CHRT (>or= 25 days per month of progestin) was associated with a higher risk of lobular breast carcinoma (OR, 2.5; 95%CI, 1.4-4.3) compared with sequential CHRT (< 25 days per month of progestin; OR, 1.5; 95%CI, 0.8-2.6). Current use of continuous CHRT was only moderately associated with risk of ductal breast carcinoma. Postmenopausal women who take CHRT appear to be at an increased risk of lobular breast carcinoma. Data from this study suggest that neither ERT use nor CHRT substantially increase the risk of ductal breast carcinoma among women age < 65 years.


Use of free scapular crest flap in pediatric epiphyseal reconstructive procedures.
Studies have been underway since 1981 on the scapular anatomic unit as a new donor site for reconstructive surgery. Anatomic studies have proven that this diaphyseal bone has a large osteocartilaginous growth epiphysis at its inferior pole, which is responsible for development of 80% of the surface of the scapula. Experimental investigations and clinical studies have revealed minimal functional limitation because of loss of the scapular crest and that its growth plate can be used beneficially for vascularized bone transfer. Four cases are reported with good results based on 2 to 14 years followup without significant impairment of the donor site.


[WHO-classification of malignant lymphomas].
Because of the multiple developmental stages of lymphocytes and the complexity of the immune system,the corresponding neoplasms, the malignant lymphomas, represent a complex group of diseases. The clinical grouping of the KIEL-classification, distinguishing high grade from low grade lymphomas, has been abandoned in the WHO-classification as it is partly misleading. Especially,mantle cell lymphoma which, according to its morphology, represents a low grade lymphoma, is characterized by an extremely aggressive clinical course. The therapy of malignant non-Hodgkin lymphomas has become more and more diverse. The great advances in survival and quality of life of patients with malignant lymphomas have been reached in multiple clinical studies to optimize therapy and simultaneously set up standards of quality for the diagnosis and therapy of malignant lymphoma (see http://www.lymphome.de). Especially in the group of so-called low grade lymphomas according to the KIEL-classification, clinical studies in Germany follow different therapy concepts for each of the diseases. Therefore,patients should be treated within such a study.


Lumbar epidural analgesia for labor in a parturient with a history of surgery for lumbar intradural ependymoma: Literature review and case presentation.
Ependymomas represent 50-60% of all brain and central nervous system tumors. Previous lumbar spine surgery for resection of an ependymoma should not be considered a relative contraindication for the administration of epidural/subarachnoid anesthesia to patients in labor. A 34-year-old G1P0, who underwent resection of an L1-L3 intramedullary ependymoma 8 years previously, presented in active labor with residual left leg numbness and tingling. The lumbar magnetic resonance imaging showed scar tissue and the L1-L3 laminectomy defect. With the acute onset of labor pain, the patient underwent continuous lumbar epidural analgesia; the epidural catheter was placed at the L5-S1 level. The patient underwent an emergency cesarean section with surgical anesthesia being attained up to a T4 dermatomal sensory level. Neuraxial anesthesia can be performed safely in patients who have previously undergone lumbar resections of intradural ependymomas. However, the anesthesiologist should place the epidural needle/catheter at a nonoperative level (e.g. above/below). Furthermore, epidural local anesthetics and opioids, as in this case, placed at the L5-S1 level below an L1-L3 prior surgical scar, may diffuse intradurally, bypassing the obliterated surgical epidural space and/or attendant scar tissue.


Therapeutic drug monitoring of vancomycin in neurosurgery patients, from trough concentration to area under the curve: a retrospective single center cohort study in a tertiary hospital.
To evaluate the effect of therapeutic drug monitoring (TDM) of vancomycin in neurosurgery patients. In this retrospective, single-center cohort study, data were collected from patients administered vancomycin after neurosurgery during 2020. Intervention by a pharmacist using an area under the curve (AUC)-based strategy for TDM of vancomycin was started on 1 July 2020. The trough concentration was monitored previously. Data regarding basic demographics, vancomycin application, and TDM were collected and analyzed. Ninety and 155 samples were included in the non-intervention and intervention groups, respectively. No difference in baseline characteristics was detected. After intervention, the attainment rate of vancomycin TDM was significantly increased from 36.7% to 52.3%. The intervention resulted in an increased daily vancomycin dose (28.9 vs. 26.7 mg/kg/day), a more reasonable sample extraction time (sixth vs. ninth dose), reductions in dose adjustments (37.4% vs. 54.4%) and preventative applications (66.7% vs. 52.3%), and no difference in kidney function impact. The intervention group had a shorter hospital stay. Intervention by a clinical pharmacist using an AUC-based strategy for vancomycin TDM can provide benefits other than pharmacokinetic attainment in neurosurgery patients. Further prospective multi-center studies are needed to establish standardized intervention measures and evaluation indicators.


Injury patterns of e-scooter-related orthopaedic trauma in central London: a multicentre study.
Electric scooters (e-Scooters) are being increasingly used in urban areas as a new means of transport. E-scooter sharing schemes have recently been piloted in the United Kingdom; however, there are no published data on orthopaedic injuries and user behaviour patterns in the UK. We aim to identify the patterns and severity of orthopaedic injuries related to e-scooter use. We performed a retrospective review of all orthopaedic referrals relating to e-scooter use from 1 March to 30 November 2020 at three hospitals, including one major trauma centre in central London. Data including patient demographics, mechanism of injury, diagnosis and treatment were collected. One hundred and five orthopaedic injuries were identified in 83 patients. The median age was 32 years and 83% were male. Seventy-nine (95.2%) patients were riders, four were pedestrians. All e-scooters were privately owned. There were 93 fractures (88.6% of total injuries noted) including 12 (12.9%) open. Fifty-two (56.0%) were upper limb fractures, 39 (41.9%) lower limb and 2 (2.1%) spinal and rib fractures. Twenty-five patients (30.1%) required an operation and 29 (34.9%) required hospital admission. Helmet use was present in 34.1%. The most common place of injury was the road (65.1%) followed by pavement (32.9%). E-scooters can cause serious injury, most commonly in males. There was an equal distribution of upper and lower limb injuries, with many associated with high-energy trauma requiring operative intervention. Helmet use was seen in one third of riders. As e-scooter use continues to increase across the UK, additional steps should be taken to ensure the safety of the riders and public.


Conjunctival Kaposi's sarcoma as the initial manifestation of acquired inmunodeficiency syndrome.
Abstract Introduction: Kaposi's sarcoma is a common neoplasm in patients with acquired immunodeficiency syndrome (AIDS). Its presentation as an initial manifestation of AIDS is very rare . To report a rare case with Kaposi's's sarcoma as an initial manifestation of AIDS. We report the case of a 37-year-old man who was a parenteral drug addict, HIV seropositive and was not under any treatment with a conjunctival lesion which was diagnosed as Kaposi's sarcoma after surgical resection. Conjunctival Kaposi's sarcoma is present frequently in HIV patients and lesions may be mistaken with other conjunctival lesions.


Apoptosis of male germ-line stem cells after laser ablation of their niche.
Male germ-line stem cells (GSCs) and their niche-the apical cells or hub cells-display a unique feature at the apices of insect testicular follicles. In the locust, Locusta migratoria, the niche consists of only one large apical cell surrounded by about 60 GSCs. The apical cell can be readily identified in the intact follicle. Using laser ablation it is feasible to destroy the apical cell exclusively without injuring neighboring GSCs or any other cells. The most immediate effect on GSCs is the loss of their structural polarity. Beginning about 3 h after laser treatment chromatin starts to clump and condense in individual GSCs, and some show the first signs of cellular breakdown. These symptoms intensify during the 96-h observation period after laser ablation of the apical cell. TUNEL staining and electron microscopic observations confirm an apoptotic cell death of the GSCs. Laser ablation of individual GSCs had no effect on neighboring GSCs or the apical cell. Destroyed apical cells were not replaced during the observation period. Mitotic divisions of GSCs ceased after about 24 h after apical cell ablation. It is speculated that it might be a general principle in stem cell-niche relationships that stem cells undergo apoptosis when the niche is dysfunctional. This could be a control mechanism to prevent tumor growth of orphaned GSCs.


The role of Automated Peritoneal Dialysis in peritoneal dialysis programme: one centre experience.
The results of the Automated Peritoneal Dialysis (APD) therapy in adult patients in the Department of Nephrology in Gdańsk during the years 1995-98 are presented. Seventeen patients (8-M, 9-F) aged 25-86 years (mean age 55.3 years), including 7 diabetics, were treated with different forms of APD. The most common indication for APD therapy was patients' loss of ability to perform Continuous Ambulatory Peritoneal Dialysis due to progressive blindness, leg amputation related to diabetic foot complications or cerebrovascular episodes (8 pts). The cumulative therapy period was 231.5 patient-months. During the observation 4 patients died, 1 received kidney transplant and 12 were still treated with APD at the end of the study. No patient was transferred to long-term hemodialysis. The peritonitis rate in the APD group was 1/57.5 patient-months. Most patients reached adequacy targets, the mean Kt/V value was 1.97 (range 1.17 - 2.36). To achieve this, 12-19 litres of dialysate were used per day (mean 14.6 L/d). There were significant differences between CCPD and NPD groups with respect to dialysis adequacy, body weight and dialysis fluid volume. We conclude that APD may be used with success in patients in whom continuation of CAPD or HD therapy is very difficult due to its complications or comorbid conditions.


Novel Bifunctional V2O3 Nanosheets Coupled with N-Doped-Carbon Encapsulated Ni Heterostructure for Enhanced Electrocatalytic Oxidation of Urea-Rich Wastewater.
Developing high performance bifunctional transition metal catalysts would be significantly beneficial for electrocatalytic oxidation of urea-rich wastewater. Herein, we synthesize a V2O3 nanosheet anchored N-doped-carbon encapsulated Ni heterostructure (Ni@C-V2O3/NF) for the reactions of urea oxidation (UOR) and hydrogen evolution (HER). Electrochemical results indicate that it exhibits small potentials of 1.32, 1.39, and 1.43 V for UOR and low overpotentials of 36, 254, and 355 mV for HER at ±10, ± 500 and ±1000 mA cm-2, respectively. It can work at 100 mA cm-2 for over 72 h as cathode and anode electrode without obvious attenuation, suggesting an outstanding durability. The reason for this behavior could be ascribed to the N-doped-carbon coating structure, the synergetic effects between Ni and V2O3, and the nano/micro nanosheets architecture self-supported on nickel foam. This work could provide a promising, inexpensive, and green method for the degradation of urea-rich wastewater and hydrogen production.


[Investigation of chronic prostatitis and altered bowel habits].
To explore the incidence, causes, and significance of altered bowel habits in chronic prostatitis. Investigating the incidence of altered bowel habits in chronic prostatitis, analyzing some possible causes to induce the symptom, such as course of disease, vegetative nerve functional disturbance, inflammation in expressed prostatic secretions, and digital rectal examination. Following up the improvement of altered bowel habits after effective treatment of chronic prostatitis. The incidence of altered bowel habits was 31.40% in 379 chronic prostatitis patients. The detected congestion and swelling of prostate was closed related to altered bowel habits in chronic prostatitis. The incidence of improvement of altered bowel habits after effective treatment of chronic prostatitis reached to 78.79%. Congestion and swelling of prostate might be the main causes for altered bowel habits in chronic prostatitis. Altered bowel habits should be considered as a common symptom and cure standard for chronic prostatitis.


Novel oral anticoagulants in chronic kidney disease: ready for prime time?
Patients with chronic kidney disease (CKD) are at increased risk of atrial fibrillation, stroke, and bleeding posing unique clinical challenges. Novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban, and apixaban have become recognized as alternative therapy to Vitamin K Antagonists (VKA) regarding the prevention of venous thromboembolism (VTE) and reduce the risk of stroke in atrial fibrillation. However, the understanding of NOACs in CKD is still underdeveloped. This review summarizes recent literature on the efficacy and safety of NOACs in patients with CKD. Studies focusing on patients with moderate kidney disease were drawn from post hoc analyses from three major NOAC trials, meta-analyses, and postmarketing surveillance studies. Cumulatively, these studies continue to demonstrate NOACs as equivalent if not superior therapies to VKAs in regards to both efficacy and safety. These studies are limited by small sample sizes as well as a lack of direct comparison between NOACs. The role of NOACs in managing VTE and atrial fibrillation is increasing. Current research suggests that NOACs are at least as efficacious and well tolerated as VKAs. More research is required to elucidate which NOAC is preferable in the clinical setting.


[Late coronary reperfusion. A possible etiology of post-infarction angina].
Late recanalisation of the infarct Related Artery is possible and may cause post-infarction angina. This was observed in 7 male patients who had complete occlusions of an artery with collateral circulation in the immediate post-infarction period. After a symptom-free period of 17 months, angina recurred and repeat angiography showed recanalisation of the occluded artery with regression of the collateral circulation resulting in myocardial ischemia. Myocardial revascularisation was then required.


Class differences in marriage and fertility among Tokugawa villagers in Mino province.
"This paper uses family reconstitution to derive indices of marriage and birth rates from observation of class differences in six villages on the Nobi plain (near Nagoya), [Japan]." The study covers the Tokugawa period, which lasted from 1603 to 1868.


"It Makes You Rethink Your Choice of the Pill": Theory-Based Formative Research to Design a Contraceptive Choice Campaign.
Half of all pregnancies in the United States remain unplanned despite improved access to highly effective long-acting reversible contraception, including the intrauterine device and the implant. This study conducted theory-based formative research to develop a contraceptive choice campaign aimed at increasing long-acting reversible contraception uptake by women ages 18-44 years in Charleston, South Carolina, an urban area in the southeastern United States. Researchers developed and tested message concepts and designs. Six focus groups and 18 interviews were conducted among reproductive-age women (n = 79). Qualitative data analysis revealed messages and designs that resonated with these women. Emphasizing long-acting reversible contraception as the healthy option, highlighting long-acting reversible contraception effectiveness, including relatable and trustworthy characters, and using language of control emerged as themes. Women reported a preference for statistics illustrating effectiveness combined with empowering messages of control over contraceptive decision making. Findings from this study offer practical recommendations for developing contraceptive choice campaigns targeting long-acting reversible contraception use and further the goal of reducing unintended pregnancy among women.


Soviet women and the autonomous family.
"The USSR family is changing in form from that of a social collectivity, a bedrock conception to socialism, to that of an autonomous family. Autonomy discloses a lack of homogeneity, an independence of choices over life-styles and a flexibility toward an interpretation given to the meaning of a socialistic state. Women are exceedingly active in making greater use of their legal rights to divorce and abortion and demanding equal status with men both in the workplace and in the home. Women are initiating major social changes, are readily adapting to changing relations and patterns in a complex society and are serving to spearhead changes in the family unit. These factors have generated major changes in the normative, behavioral and structural dimensions of marriage and family life in the Soviet Union."


Biomolecular filters for improved separation of output signals in enzyme logic systems applied to biomedical analysis.
Biomolecular logic systems processing biochemical input signals and producing "digital" outputs in the form of YES/NO were developed for analysis of physiological conditions characteristic of liver injury, soft tissue injury, and abdominal trauma. Injury biomarkers were used as input signals for activating the logic systems. Their normal physiological concentrations were defined as logic-0 level, while their pathologically elevated concentrations were defined as logic-1 values. Since the input concentrations applied as logic 0 and 1 values were not sufficiently different, the output signals being at low and high values (0, 1 outputs) were separated with a short gap making their discrimination difficult. Coupled enzymatic reactions functioning as a biomolecular signal processing system with a built-in filter property were developed. The filter process involves a partial back-conversion of the optical-output-signal-yielding product, but only at its low concentrations, thus allowing the proper discrimination between 0 and 1 output values.


A di-leucine motif and an upstream serine in the interleukin-6 (IL-6) signal transducer gp130 mediate ligand-induced endocytosis and down-regulation of the IL-6 receptor.
The interleukin-6 (IL-6) receptor complex is composed of two different subunits, the IL-6 binding protein (IL-6R, gp80) and the signal transducing component gp130. Our previous studies revealed that the 10-amino acid sequence TQPLLDSEER within the intracellular domain of gp130 is crucial for the efficient internalization of IL-6. Since this sequence contains a putative di-leucine internalization motif, we further analyzed this region by constructing two additional deletions and a series of point mutants. Analyses of these mutants showed that the di-leucine pair (Leu-145 and Leu-146) is essential for ligand internalization, with leucine 145 being less resilient to exchanges. Furthermore, when a chimeric protein (Tac-STQPLL) composed of the Tac antigen fused to the hexapeptide STQPLL of gp130 was studied, we found that this sequence is sufficient to mediate endocytosis and lysosomal targeting of the chimera. Mutational analysis of three serine residues upstream of the di-leucine motif revealed that mutation of serine 139 to an alanine reduces the initial internalization rate by 50%. This finding suggests that a serine phosphorylation may be important for rapid endocytosis.


Gender and age differences in plasma carnitine, muscle strength, and exercise tolerance in haemodialysis patients.
Haemodialysis patients have impaired exercise tolerance that may be related to impaired carnitine availability and/or alterations in carnitine metabolism. As carnitine metabolism is sex- and age-related, we examined plasma free and esterified carnitine concentrations, muscle strength, and estimated exercise tolerance in female (n=51) and male (n=63) patients of different ages (18-86 years). Concentrations of free carnitine and acetylcarnitine were determined in the plasma of patients. Isometric handgrip strength was measured using a dynamometer while exercise tolerance was predicted from scores for self-reported walking distance on the level and on an incline. Plasma total carnitine concentration in the females was significantly lower than that of males (35.4+/-1.3 and 42.4+/-1.4 micro mol/l, respectively, P<0.01). This was almost entirely due to the lower plasma free carnitine concentration of females when compared with the males (20.6+/-0.9 and 26.3+/-1.1 micro mol/l, respectively, P<0.05). Furthermore, plasma free carnitine concentrations were negatively correlated with age in females (r=-0.45, P<0.001) even when the linear effects of haemoglobin, albumin, body weight, time on dialysis, and muscle strength were removed from the regression analysis (partial correlation coefficient; pcc=-0.43, P=0.018), but not in the males (r=0.03, P>0.05). Isometric handgrip strength and estimated exercise tolerance on the level were lower in females than males (138.9+/-10.9 and 259.0+/-15.2 N, P<0.001; and 3.5+/-0.2 and 4.3+/-0.2, P<0.05, respectively). Isometric handgrip strength and estimated exercise tolerance (walking distance on the level and on an incline) were positively correlated with plasma free carnitine concentrations in females, but not in the males. There was a strong relationship between plasma free carnitine concentrations and age in female patients, but not in males. It is unlikely that the reduction in plasma free carnitine in females was a direct causative factor in their reduced exercise tolerance, but probably reflects greater muscle de-conditioning/atrophy with age in female patients.


Safety and efficacy of low-dose methotrexate for pediatric patients with steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation.
Low-dose methotrexate (LD-MTX) has long been included in prophylaxis regimens for acute graft-versus-host disease (aGVHD). In addition, LD-MTX is expected as a treatment option to control aGVHD by regulating the cytokine network. In this study, we retrospectively evaluated 35 patients with steroid-refractory acute GVHD to evaluate the safety and efficacy of LD-MTX as a salvage treatment. LD-MTX was administered weekly at a dose of 10 mg/m(2). Overall, 13 patients (37 %) achieved complete response and three (9 %) achieved partial response within 4 weeks after LD-MTX was initiated without any additional agents. Resolution of manifestations of aGVHD in each evaluable organ was observed in 12 of the 23 cases (52 %) with skin aGVHD and in eight of the 23 cases (35 %) with GI aGVHD. Neutropenia and thrombocytopenia (grades III and IV) were observed in nine (26 %) and 17 patients (49 %), respectively. Fatal infectious complications occurred in only three patients (9 %) after LD-MTX treatment. Of the 35 patients studied, 22 were alive with a median follow-up of 60 months and an overall survival rate (Kaplan-Meier estimate) was 62 %. LD-MTX seems suitable for salvage therapy and will not increase risk of infection. Further evaluation of the use of LD-MTX as salvage therapy for steroid-refractory acute GVHD is warranted.


Temporary vascular continuity during damage control: intraluminal shunting for proximal superior mesenteric artery injury.
"Damage control" is an accepted technique for the treatment of the patient with exsanguinating injuries to the abdomen and intraoperative coagulopathy. We describe the use of an intraluminal shunt to maintain temporary vascular continuity of the superior mesenteric artery during rewarming and correction of coagulopathy in the intensive care unit following a gun shot wound to the abdomen. Successful complex reconstruction was achieved at definitive laparotomy using an autogenous vein interposition graft.


Mezlocillin enteral absorption in rabbits.
To determine the role of enterohepatic recirculation on its nonlinear elimination, we studied the enteral absorption of mezlocillin in rabbits. Mezlocillin was not substantially absorbed from the stomach or duodenum. We conclude that enterohepatic recirculation does not cause the dose-dependent elimination kinetics of mezlocillin.


Plume expansion dynamics of matrix-assisted laser desorption ionization.
High-resolution angular and velocity distributions for neutral analytes (tryptophan and poly-tryptophan) and matrix (2,4,6-trihydroxyacetophenon, THAP) are measured by using 355 nm laser desorption. The information suggests that two separate mechanisms dominate the angular and velocity distributions at the beginning and before the end of desorption. A molecular jet-like isentropic expansion dominates the plume expansion at the beginning of desorption. This only occurs at high surface temperature, thus resulting in a large velocity normal to the surface and a very narrow angular distribution. Most of the analytes are produced under these conditions. Before the end of desorption, the surface temperature decreases and the mechanism of thermal desorption at low vapor pressure takes over. The velocities become small and the angular distribution is close to cosθ. Only a very small amount of analytes are generated under these conditions. Compared to tryptophan, poly-tryptophan has a much narrower angular distribution, thereby suggesting that it is only produced at the higher surface temperatures.


Alpha-fluoromethylhistidine decreases the Leu-enkephalinamide- and morphine-induced corticosterone response in rats.
The effect of inhibition of brain histamine synthesis by alpha-fluoromethylhistidine (alpha-FMH) on the pituitary adrenocortical activity stimulated by D-Ala-D-Leu-enkephalinamide (DADL) and morphine was investigated indirectly through corticosterone secretion in conscious rats. alpha-FMH (20 mg/kg i.p.) drastically reduced the whole brain histamine content, measured 2 h later. The same pretreatment also considerably reduced the corticosterone response to morphine given intraperitoneally. When alpha-FMH was administered intracerebroventricularly (50 micrograms), the maximum inhibition of the corticosterone response to DADL and morphine occurred 4 h after administration, which may suggest a weaker accessibility of alpha-FMH from the cerebral ventricle to the brain structures involved in pituitary-adrenocortical stimulation. The corticosterone responses were not related to the core temperature changes. These results indicate that inhibition of brain histamine synthesis by alpha-FMH considerably impairs the pituitary-adrenocortical response to the opioid delta- and mu-receptor agonists DADL and morphine. They also suggest that neuronal histamine is significantly involved in the central stimulation of the pituitary-adrenal axis by opioids.


Suberization: inhibition by washing and stimulation by abscisic Acid in potato disks and tissue culture.
Wounding of potato (Solanum tuberosum L.) tubers results in suberization, apparently triggered by the release of some chemical factor(s) at the cut surface. Suberization, as measured by diffusion resistance of the tissue surface to water vapor, was inhibited by mm concentrations of indoleacetic acid, unaffected by mm concentrations of traumatic acid, severely inhibited at mum concentrations of cytokinin, but stimulated by abscisic acid (ABA) at 10(-4)m. Thorough washing of potato disks up to 3 to 4 days after cutting resulted in severe inhibition of suberization as measured both by diffusion resistance and by the amount of the octadecene diol generated by hydrogenolysis (LiAlH(4)) of the tissue. Disks washed after 4 days did not show any inhibition of suberization. High performance liquid chromatographic analysis of the wash from fresh potato disks showed that about 14 ng of ABA was released into the wash per g of tissue. The amount of ABA released increased with time up to 4 to 6 hours of washing. The maximal amount of ABA was washed out after aging for 24 hours and after 2 days of aging ABA could no longer be found in the surface wash of the disks. Addition of ABA to the media of potato tissue cultures resulted in suberin formation whereas control cultures contained little suberin. The effect of ABA on suberization in the tissue cultures was shown to be linearly concentration-dependent up to 10(-4)m and a linear increase in suberin formation was seen up to about 8 days of culture growth on the media containing 10(-4)m ABA. From these results it is proposed that during the early phase of wound-healing ABA plays a role in triggering a chain of biochemical processes which eventually (in about 3 to 4 days) result in the formation of a suberization-inducing factor, responsible for the induction of the enzymes involved in suberin biosynthesis.


[Anesthesia risks].
Both effects of anaesthesia and analgesia are involved in the anaesthesia risk. Most often, anaesthetic accidents appear to be related to hypoxia. Applying anaesthetic security principles allow controlling risk. Systematic use and check of monitoring instruments and anaesthesiology department organisation appear as major preventive measures. Independent operative risk is related to individual, surgical and anaesthetic factors, which interact with one another. Individual preoperative evaluation is one of the great challenges of anaesthesiology. The establishment of an aimed perioperative anaesthetic strategy is the best warrant of the operative risk reduction. Assessment of individual benefit to risk ratio takes also into account the experience of the surgeon and anaesthesiologist. It implicates the patient's choice as well his general practitioner as a privileged advice.


The impact of legislation on divorce: a hazard function approach.
"The paper examines the impact of the introduction of no-fault divorce legislation in Australia. The approach used is rather novel, a hazard model of the divorce rate is estimated with the role of legislation captured via a time-varying covariate. The paper concludes that contrary to U.S. empirical evidence, no-fault divorce legislation appears to have had a positive impact upon the divorce rate in Australia."


Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats.
Tetramethylpyrazine (TMP) has been used to treat ischemic stroke. However, scientific evidence related to its effectiveness or precise modes of neuroprotective action is largely unclear. This study provides evidence of an alternative target for TMP and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of TMP on intracerebral cellular inflammatory response in a rat model of permanent cerebral ischemia. TMP exhibited a neuroprotective effect against ischemic deficits by reduction of behavioral disturbance, brain infarction, and edema. The results of immunohistochemistry, enzymatic assay, Western blot, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and flow cytometric analysis revealed that TMP reduced the percentages of activated macrophages/microglia and infiltrative lymphocytes, neutrophils, and macrophages and pro-inflammatory cytokine expression after cerebral ischemia. In parallel with these immunosuppressive phenomena, TMP also attenuated the activities of ischemia-induced inflammation-associated signaling molecules and transcription factors. Another finding in this study was that the anti-inflammatory and neuroprotective effects of TMP were accompanied by a further elevated expression of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in ipsilateral neurons and macrophages/microglia after cerebral ischemia. Taken together, our results suggest that both the promotion of endogenous defense capacity and the attenuation of the extent and composition percentage of the major cellular inflammatory responses via targeting of macrophages/microglia by elevating Nrf2/HO-1 expression might actively contribute to TMP-mediated neuroprotection against cerebral ischemia.


A focus group inquiry into the perceptions of primary health care teams and the provision of health care for adults with a learning disability living in the community.
This study addresses the primary health needs of adults with learning disabilities living in the community. Policies specific to this client group and incorporating the ideology of normalization are noted and evidence of their implementation is sought. Previous research suggests that the adoption of a social rehabilitative model of care may have resulted in the neglect of health care needs. The recent closure of a local, subnormality hospital provided a critical situation and context for the study. The research question is, how do primary health care teams perceive the needs of adults with learning disabilities living in the community, and are they meeting their needs? Three primary health care teams formed the sample and data were obtained through semi-structured, focus group interviews. A conceptual framework developed early in the study influenced both the interview guide and the data analysis. The study suggests that practitioners working within primary health care teams have a limited awareness of the health care needs of adults with learning disabilities. Contributing factors were identified and include: negative attitudes towards the concept of normalization; inadequate education; a shortfall in financial and human resources; and poor collaboration with the specialist team.


Understanding, justifying, and finding oneself.
This essay tries to explain some ways in which we can come to know about ourselves, in particular about what we think. It also tries to distinguish what we are and think from what we ought to be and think.


Teenage pregnancy in adolescents with an incarcerated household member.
This study examines the association between the incarceration of a household member and adolescent pregnancy, and evaluates whether this association extends beyond that of other variables associated with sexual health. We used data from 12 waves of the National Longitudinal Survey of Youth: Child and Young Adult. After eliminating males and individuals who did not respond to key questions, a sample of 1,229 girls (ages 14-19) was analyzed. Girls who experienced the incarceration of a household member faced more demographic and family environment risk factors than those who did not. Regression analyses demonstrated that the addition of a household incarceration variable afforded superior prediction of teenage pregnancy relative to the prediction based on demographic and family features alone. Programs that are directed toward reducing teen pregnancy will benefit from attention to the home situation of the at-risk girl, particularly the experience of household member incarceration and related family dynamics.


Mass spectrometric studies of the path of carbon in photosynthesis: positional isotopic analysis of (13)C-labelled C(4) to C(7) sugar phosphates.
The (EIMS) electron ionization mass spectrometric fragmentation patterns of the methoxime- and ethoxime-trimethylsilyl (TMS) derivatives of C(4) to C(7) sugars involved as phosphates in the Calvin pathway of photosynthesis in plants were analysed by gas chromatography/EIMS using specifically labelled (13)C analogs. In general, most but not all of the major ions in the mass spectra arise from single carbon-carbon bond cleavages of the straight-chain derivatives. The results confirm that GC/MS of the alkoxime-TMS derivatives is a viable method for measuring (13)C incorporations at individual carbon atoms in each of the sugar phosphates during photosynthetic experiments with (13)CO(2).


Household Registration System, Migration, and Inequity in Healthcare Access.
This study investigates the influence of the household registration system on rural-urban disparity in healthcare access (including healthcare quality, blood pressure check, blood test, vision test, dental examination, and breast exam), using data from a large-scale nationwide life history survey that covered 150 counties across 28 provinces and municipalities in China. In contrast to the findings of many previous studies that emphasize the disparity in the residence place as the cause of rural-urban disparity in healthcare access, this study finds that the residence place just has a very limited influence on healthcare access in China, and what really matters is the household registration type. Our empirical results show that people with a non-rural household registration type generally have better healthcare access than those with a rural one. For rural residents, changing the registration type of their household (from rural to non-rural) can improve their healthcare access, whereas changing the residence place or migrating from rural to urban areas have no effect. Therefore, mere rural-to-urban migration may not be a valid measure to eliminate the rural-urban disparity in healthcare access, unless the institution of healthcare resource allocation is reformed.


Aluminum salts stimulate luminol-enhanced chemiluminescence production by human neutrophils.
Aluminum intoxication is currently thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations seen during long-term hemodialysis and aging. The hypothesis that aluminum toxicity is mediated via an increased free radical production was tested by studying the effects of two aluminum and five other metallic compounds on the production of luminol-enhanced chemiluminescence (LECL) by human neutrophils. AlCl3, Al2(SO4)3 and FeCl3 were found to stimulate LECL production by human neutrophils whereas FeCl2, CuCl, CuCl2, AuCl3 were inactive. Metal chelators such as Desferal, EDTA and DETAPA suppressed aluminum-induced stimulation and depressed cell-dependent LECL below basal levels. Sodium azide and Cytochalasin B greatly depressed both basal and aluminum-induced stimulation of LECL production, suggesting that, in this system, most of this stimulation was due to myeloperoxidase. These results suggest that high tissue aluminum concentrations may induce cell-tissue lesions by stimulating local production or release of mediators of tissue damage.


Probiotics for treating eczema.
Eczema is a common chronic skin condition. Probiotics have been proposed as an effective treatment for eczema; their use is increasing, as numerous clinical trials are under way. This is an update of a Cochrane Review first published in 2008, which suggested that probiotics may not be an effective treatment for eczema but identified areas in which evidence was lacking. To assess the effects of probiotics for treating patients of all ages with eczema. We updated our searches of the following databases to January 2017: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, the Global Resource of Eczema Trials (GREAT) database, MEDLINE, Embase, PsycINFO, the Allied and Complementary Medicine Database (AMED), and Latin American Caribbean Health Sciences Literature (LILACS). We searched five trials registers and checked the reference lists of included studies and relevant reviews for further references to relevant randomised controlled trials (RCTs). We also handsearched a number of conference proceedings. We updated the searches of the main databases in January 2018 and of trials registries in March 2018, but we have not yet incorporated these results into the review. Randomised controlled trials of probiotics (live orally ingested micro-organisms) compared with no treatment, placebo, or other active intervention with no probiotics for the treatment of eczema diagnosed by a doctor. We used standard methodological procedures as expected by Cochrane. We recorded adverse events from the included studies and from a separate adverse events search conducted for the first review. We formally assessed reporting bias by preparing funnel plots, and we performed trial sequential analysis for the first primary outcome - eczema symptoms at the end of active treatment.We used GRADE to assess the quality of the evidence for each outcome (in italic font). We included 39 randomised controlled trials involving 2599 randomised participants. We included participants of either gender, aged from the first year of life through to 55 years (only six studies assessed adults), who had mild to severe eczema. Trials were undertaken in primary and secondary healthcare settings, mainly in Europe or Asia. Duration of treatment ranged from four weeks to six months, and duration of follow-up after end of treatment ranged from zero to 36 months. We selected no standard dose: researchers used a variety of doses and concentrations of probiotics. The probiotics used were bacteria of the Lactobacillus and Bifidobacteria species, which were taken alone or combined with other probiotics, and were given with or without prebiotics. Comparators were no treatment, placebo, and other treatments with no probiotics.For all results described in this abstract, the comparator was no probiotics. Active treatment ranged from six weeks to three months for all of the following results, apart from the investigator-rated eczema severity outcome, for which the upper limit of active treatment was 16 weeks. With regard to score, the higher the score, the more severe were the symptoms. All key results reported in this abstract were measured at the end of active treatment, except for adverse events, which were measured during the active treatment period.Probiotics probably make little or no difference in participant- or parent-rated symptoms of eczema (13 trials; 754 participants): symptom severity on a scale from 0 to 20 was 0.44 points lower after probiotic treatment (95% confidence interval (CI) -1.22 to 0.33; moderate-quality evidence). Trial sequential analysis shows that target sample sizes of 258 and 456, which are necessary to demonstrate a minimum mean difference of -2 and -1.5, respectively, with 90% power, have been exceeded, suggesting that further trials with similar probiotic strains for this outcome at the end of active treatment may be futile.We found no evidence suggesting that probiotics make a difference in QoL for patients with eczema (six studies; 552 participants; standardised mean difference (SMD) 0.03, 95% CI -0.36 to 0.42; low-quality evidence) when measured by the participant or the parent using validated disease-specific QoL instruments.Probiotics may slightly reduce investigator-rated eczema severity scores (24 trials; 1596 participants). On a scale of 0 to 103 for total Severity Scoring of Atopic Dermatitis (SCORAD), a score combining investigator-rated eczema severity score and participant scoring for eczema symptoms of itch and sleep loss was 3.91 points lower after probiotic treatment than after no probiotic treatment (95% CI -5.86 to -1.96; low-quality evidence). The minimum clinically important difference for SCORAD has been estimated to be 8.7 points.We noted significant to extreme levels of unexplainable heterogeneity between the results of individual studies. We judged most studies to be at unclear risk of bias; six studies had high attrition bias, and nine were at low risk of bias overall.We found no evidence to show that probiotics make a difference in the risk of adverse events during active treatment (risk ratio (RR) 1.54, 95% CI 0.90 to 2.63; seven trials; 402 participants; low-quality evidence). Studies in our review that reported adverse effects described gastrointestinal symptoms. Evidence suggests that, compared with no probiotic, currently available probiotic strains probably make little or no difference in improving patient-rated eczema symptoms. Probiotics may make little or no difference in QoL for people with eczema nor in investigator-rated eczema severity score (combined with participant scoring for eczema symptoms of itch and sleep loss); for the latter, the observed effect was small and of uncertain clinical significance. Therefore, use of probiotics for the treatment of eczema is currently not evidence-based. This update found no evidence of increased adverse effects with probiotic use during studies, but a separate adverse events search from the first review revealed that probiotic treatment carries a small risk of adverse events.Results show significant, unexplainable heterogeneity between individual trial results. Only a small number of studies measured some outcomes.Future studies should better measure QoL scores and adverse events, and should report on new probiotics. Researchers should also consider studying subgroups of patients (e.g. patients with atopy or food allergies, adults) and standardising doses/concentrations of probiotics given.


Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.
Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.


Lived Experiences of Long-Term Care Administrative Staff Responsible for the Admissions Process.
The process of admission of, typically, older residents into long-term care (LTC) has been greatly examined from the perspectives of the residents and their family members/caregivers. However, the viewpoint of the administrative staff directly involved has been left relatively unexamined. This article highlights findings from a qualitative study focused on exploring the lived experiences of LTC administrative staff working with residents-to-be and families/caregivers during the admissions process. Data from semi-structured interviews with seven participants indicate that these individuals often take on roles/tasks that go beyond the scope of their official work descriptions. Participants acknowledged the heavy toll of the stressful nature of their work on their health/well-being, but often normalized the pressures as part of their professional, if not personal, responsibilities to help others. Recommendations on improving the admissions process highlighted the lack of critique of the LTC system, despite its responsibility for the challenges that shape their day-to-day work.


Absence of the frequently reported PIK3CA, CASP8, and NOTCH1 mutations in South Indian oral cancers.
Somatic mutations of the PIK3CA, CASP8, and NOTCH1 have been frequently detected in various human cancers. Our study aimed to analyze the mutational status of these genes in South Indian oral cancers. We performed mutational analysis of the PIK3CA (exons 9 and 20), CASP8 (exon 9), and NOTCH1 (exons 5, 6, 7, 8, and 9) genes in 96, 48, and 44 oral cancer samples, respectively. All the specified exons were PCR (polymerase chain reaction)-amplified and directly sequenced by Sanger sequencing. PIK3CA gene mutations were not found; however, a synonymous single nucleotide polymorphism (SNP) [rs17849079] was observed frequently [35/96 (36.4%)] in oral cancer samples. Further, no mutations were detected in the CASP8 gene, but observed a frequent [32/48 (66.6%)] SNP [rs1045487] in the oral cancer samples. We did not detect any mutation in the NOTCH1 gene (exons 5, 6, 7, 8, and 9) in all the [0/44] analyzed oral cancer samples. This is the first study that reports the status of the PIK3CA, CASP8, and NOTCH1 mutations in South Indian oral cancer samples. Our study suggests that either mutations in these genes are uncommon in South Indian oral cancer samples or likely other genes in this pathway might be mutated.


Teaching clinical methods to medical students.
This paper demonstrates that it is feasible to teach clinical methods in general practice and describes the organization of an appropriate attachment. Willing practitioners, properly briefed, are competent to undertake clinical methods teaching and the attachment provides satisfaction to both students and teachers. It is possible to provide in primary care the elements which seem to be the key to this outcome--protected time, teaching in very small groups, direct observation and concentration on systematic examination rather than on particular physical signs. There is a strong case for the promoting of clinical methods teaching by general practitioners.


Identification of pathogenic Vibrio species by multilocus PCR-electrospray ionization mass spectrometry and its application to aquatic environments of the former soviet republic of Georgia.
The Ibis T5000 is a novel diagnostic platform that couples PCR and mass spectrometry. In this study, we developed an assay that can identify all known pathogenic Vibrio species and field-tested it using natural water samples from both freshwater lakes and the Georgian coastal zone of the Black Sea. Of the 278 total water samples screened, 9 different Vibrio species were detected, 114 (41%) samples were positive for V. cholerae, and 5 (0.8%) samples were positive for the cholera toxin A gene (ctxA). All ctxA-positive samples were from two freshwater lakes, and no ctxA-positive samples from any of the Black Sea sites were detected.


Cloning of Mongolian gerbil cDNAs encoding inflammatory proteins, and their expression in glandular stomach during H. pylori infection.
Mongolian gerbils are considered to be a good animal model for understanding the development of Helicobacter pylori-associated diseases. However, limitations regarding the genetic information available for this animal species hamper the elucidation of underlying mechanisms. Thus, we have focused on identifying the nucleotide sequences of cDNAs encoding Mongolian gerbil inflammatory proteins, such as interleukin-1 (IL-1beta), tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, we examined the mRNA expression of these genes in the glandular stomach by RT-PCR at 1-8 weeks after H. pylori infection. The deduced amino acid homologies to mouse, rat and human proteins were 86.2%, 83.6% and 67.8% for IL-1beta, 87.2%, 85.1% and 78.4% for TNF-alpha , 91.9%, 90.2% and 84.8% for COX-2 and 90.8%, 89.1% and 80.1% for iNOS, respectively. The average stomach weight of Mongolian gerbils inoculated with H. pylori was increased in a time-dependent manner at 1, 2, 4 and 8 weeks after inoculation. In the pyloric region, mRNA expression levels of IL-1beta, TNF-alpha and iNOS were increased in H. pylori-infected animals at the 2 weeks time point, while in the fundic region, expression levels of IL-1beta, TNF-alpha and iNOS were elevated at 4 and 8 weeks. The COX-2 expression level in the fundic region was clearly elevated in infected animals compared with control animals at 4 and 8 weeks, but in the pyloric region, expression levels were similar in both infected and control animals. Thus, our results indicate that oxidative stress occurs from an early stage of H. pylori infection in the glandular stomach of Mongolian gerbils.


Beneficial effects of intravenous pamidronate treatment in children with osteogenesis imperfecta under 24 months of age.
Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility and low bone mass. Low bone density and fracture is a cause of morbidity. Limited data exists on bisphosphonate treatment in patients under 24 months of age. The objective of the study was to examine the safety and efficacy of pamidronate in children under 24 months with OI. To do so, we carried out a retrospective chart review and analysis of OI patients started on intravenous pamidronate under 24 months of age. Pamidronate was administered in three-day cycles. Growth, the number of fractures, and lumbar bone mineral densities were recorded both prior to and after treatment initiation. A total of 18 patients were reviewed. Five were classified as OI type I, seven were type III, and six were type IV. The mean age at treatment initiation was 12 months (range 11 days to 23 months). The mean lumbar z score at baseline was -3.63, which improved to -1.53 at one year (P < 0.01) and 0.79 (P < 0.01) at the end of the study. The fracture rate improved from 68 fractures in 209 months (0.32 fractures/patient-month) before treatment to 41 fractures in 1,248 months (0.03 fractures/patient-month) post-treatment (P < 0.05). Height standard deviation score (SDS) was conserved from baseline to end of study (-2.12 ± 2.45 vs. -2.45 ± 2.73) (P = 0.05) with an average follow-up of 73 months. The only adverse effect recorded in six infants was fever during the initial pamidronate infusion. Treatment with intravenous pamidronate is safe, significantly improves lumbar bone mineral density (L-BMD), and reduces fracture rates in young infants with OI while preserving linear growth.


One-step real-time RT-PCR for pandemic influenza A virus (H1N1) 2009 matrix gene detection in swine samples.
In the spring of 2009, a novel (H1N1) influenza A virus began to spread among humans worldwide. Although the 2009 H1N1 is related genetically to swine influenza viruses, human infection has not been connected to pig exposure. Because the virus is now circulating widely in the human population, swine herds are at increased risk of becoming infected. In order to investigate potential outbreaks of the 2009 pandemic virus in pigs, a quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) for the detection of the (H1N1) 2009 RNA in clinical specimens was developed. To evaluate the applicability of the test as a diagnostic tool in the screening of field specimens from swine, 64 field isolates of North American swine, 5 equine and 48 avian influenza viruses collected during diagnostic investigations were analyzed retrospectively as well as samples collected during an experimental in vivo infection with two novel H1N1 isolates, A/California/04/2009 (H1N1)v virus and A/Mexico/4108/2009 (H1N1)v. The sensitivity of the qRT-PCR was shown to be higher with respect to standard techniques such as virus isolation and the reproducibility was satisfactory. The present unique and highly sensitive assay is able to detect as little as 1 x 10(1) copies of RNA per microl of template and it represents a rapid and useful approach for the screening and quantitation of (H1N1) 2009 RNA in porcine specimens.


Beneficial effects of clonidine on severe self-injurious behavior in a 9-year-old girl with pervasive developmental disorder.
We report the successful treatment of persistent self-injurious behavior (SIB) in a 9-year-old girl with pervasive developmental disorder. The girl had inflicted severe tissue damage to her face, neck, and inner thighs due to pinching, scratching, and rubbing of her skin. Using a rating scale to quantify surface tissue damage produced by SIB, the number of bodily injuries, the intensity of skin trauma, and the projected risk of further physical harm decreased dramatically following the administration of clonidine that was titrated to a maximum dose of 0.4 mg daily. The girl's SIB showed marked improvement over a 24-month period of observation. Issues related to pharmacotherapy of SIB using alpha adrenergic agonists are discussed.


Barriers to suicide risk management in clinical practice: a national survey of oncology nurses.
Standards of practice identify the nurse's pivotal role in risk detection, assessment, intervention, and management of suicidal patients, but scant research explores the barriers that hinder this role. This study describes the analysis of barriers to suicide risk management from a survey of a random sample of members of a national organization, the Oncology Nursing Society (n = 1200), who participated in a descriptive study exploring nurses' knowledge and attitudes about suicide. The 454 (37%) respondents included respondents from the United States, Canada, and Puerto Rico. Instruments included a demographic inventory, the Suicide Opinion Questionnaire (SOQ), a suicide attitude measure (SUIATT), and a vignette of a suicidal patient. Nurses knew an average of 4.8 out of 9 suicide risk factors and 49.4% miscalculated the risk of suicide. In contrast with their moderate to high ratings of suicide risk, they indicated minimal interventions. Barriers to management of suicidal patients included deficits in skill, knowledge, referrals, patient teaching, advocacy, or consultation as well as participants' and religious/other values, uncomfortable feelings, personal experiences, and the weight of professional responsibility. Strategies for intervention include: suicide prevention education, consultation, values clarification, ethical analysis, and conflict resolution and psychosocial support to reduce barriers. Nurses are not alone in their request for more education about suicide prevention; this study confirms earlier research of psychologists and psychiatrists who report they need more education in suicide risk management.


Legal issues in emergency radiology. Practical strategies to reduce risk.
Various joint commission and individual state standards affect emergency radiology practice and have legal implications. The ACEP has entered the burgeoning field of practice guidelines; fortunately, their practice guideline preparation system is arguably the most thorough in medicine at this time. This is of great importance to emergency physicians, because practice guidelines are not without their own potential legal, educational, and compliance problems. Trends toward cost-reduction through reduced radiograph utilization are a real phenomenon in all of medicine. It remains to be seen if costs can be reduced without increasing legal exposure. Excellent clinical guidelines are helpful to emergency physicians. The Massachusetts ACEP model, which appears to effectively blend closed claim data into practice guidelines, has built-in educational support and compliance incentives. This model may become a national standard in the future. Pediatric radiology risk management issues, such as the statute of limitations, have been discussed. Emergency physicians should be knowledgeable about the most commonly missed pediatric emergency radiologic diagnoses. Some aspects of common emergency radiology practice patterns are of relevance to a discussion of risk management in emergency radiology. Issues such as emergency physician radiograph interpretation responsibilities and follow-up systems emerge repeatedly in malpractice claims. The use of CQI strategies may prove helpful in improving practice patterns. Communication between emergency physician and radiologists is critical. Good communication requires the development of good rapport and should pay dividends in improved patient care.


Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment.
Adrenocortical carticnoma (ACC) is a rare malignancy with an incidence of 0.7-2.0 cases/million habitants/year. The diagnosis of malignancy relies on careful investigations of clinical, biological, and imaging features before surgery and pathological examination after tumor removal. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC is initially diagnosed incidentally. After the diagnosis, in order to assess the ACC prognosis and establish an adequate basis for treatment decisions different tools are proposed. The stage classification proposed by the European Network for the Study of Adrenal Tumors (ENSAT) is recommended. Pathology reports define the Weiss score, the resection status and the proliferative index, including the mitotic count and the Ki67 index. As far as the treatment is concerned, in case of tumor limited to the adrenal gland, the complete resection of the tumor is the first option. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Recently, the First International Randomized (FIRM-ACT) Trial in metastatic ACC reported the association between mitotane and etoposide/doxorubicin/cisplatin (EDP) as the new standard in first line treatment of ACC. In last years, new targeted therapies, including the IGF-1 receptor inhibitors, have been investigated, but their efficacy remains limited. Thus, new treatment concepts are urgently needed. The ongoing "omic approaches" and next-generation sequencing will improve our understanding of the pathogenesis and hopefully will lead to better therapies.


Spectrofluorometric determination of the toxic constituents of Cleistanthus collinus.
Spectrofluorometric quantitation of a lignan lactone, diphyllin, and its glycosides cleistanthin A and cleistanthin B, the active principles of the poisonous plant Cleistanthus collinus, is reported for the first time. Thin layer chromatographic resolution of the components precedes the fluorometric measurements. The method is highly reproducible and sensitive to 0.1 microgram/mL for diphyllin and to 1 microgram/mL for cleistanthins A and B in ethanol. The technique is employed for the assay of several biospecimens of forensic and clinical importance.


Assessing temporal variability and controlling factors of the sediment budget of a small agricultural catchment in Northern France (the Pommeroye).
A high-frequency monitoring station was implemented at the outlet of the small catchment of the Pommeroye (0.54 km2) in Northern France to study erosion by runoff and hydro-sedimentological responses to heavy rainfall events in the context of Quaternary loess deposits. The aim of this experimental work is to assess the temporal variability of sediment yield and to identify the factors controlling the hydro-sedimentary response. To achieve this goal, statistical and hydro-sedimentary dynamic analyses were performed. During two years of monitoring (April 2016-April 2018), 48 flood events were recorded. The specific sediment yield (SSY) is highly variable and was evaluated to 29.4-70 t km-2 yr-1 which is conventional for the study region. Most of the sediment yield was produced in winter (55%) and autumn (42%). Only 3% of SSY were produced during spring and summer periods. According to our results, only 6% of the erosive events are responsible for the transport of more than 40% of the sediment flux recorded at the outlet. This underlines the temporal variability of the hydro-sedimentary production in small agricultural catchments for which most of the hydro-sedimentary flux is produced during a limited number of events. The results of statistical analyses show that the total amount of rainfall and the duration of a rainfall episode are the main controlling factors on the hydro-sedimentary response. Our results also suggest that the rainfall kinetic energy better reflects the sediment detachment, and that the 48 h-antecedent rainfall is not linked to the hydro-sedimentary response.


Rhinitis and disseminated disease in a ferret (Mustela putorius furo) naturally infected with Sarcocystis neurona.
Naturally occurring Sarcocystis neurona infection in a ferret (Mustela putorius furo) with rhinitis and disseminated disease are described for the first time. The ferret exhibited severe rhinitis with intra-lesional S. neurona merozoites and schizonts. Diagnosis was confirmed immunohistochemically by staining with S. neurona-specific antibodies, and by phylogenetic analyses of conserved and variable portions of nuclear ribosomal DNA. On the basis of intense schizogony in the nasal mucosa, we propose the possibility of an olfactory nerve pathway route of infection for S. neurona meningoencephalitis.


Development and validation of a culturally appropriate HIV/AIDS Stigma Scale for Puerto Rican health professionals in training.
HIV/AIDS stigma continues to be an obstacle for primary and secondary HIV prevention. Its consequences for the lives of people living with the disease have been well documented and continue to be of great concern for health care providers and researchers in the field. These consequences are worsened when such stigma emanates from health professionals, as this can limit access to services. One of the main obstacles for HIV/AIDS stigma research in Puerto Rico is the absence of quantitative measures to assess HIV/AIDS stigma manifestations among health professionals. In light of this gap in the scientific literature, the main objective of this study was to develop and test the psychometric properties of a culturally appropriate HIV/AIDS Stigma Scale for Puerto Rican health care providers and to develop a reduced form of the scale suitable for use in time-limited clinical settings. The developed measure was based on previous qualitative evidence gathered from Puerto Rican health professionals (Varas-Diaz, Serrano-Garcia, & Toro-Alfonso, 2005) and administered to a sample of 421 health professionals in training. The scale addresses 12 HIV/AIDS stigma dimensions. In quantitative analyses 11 of these dimensions demonstrated satisfactory validity and reliability. These dimensions in turn were subcomponents of a higher-order general stigma factor. Implications and limitations of these findings are discussed.


Risk of transmission of carbapenem-resistant Enterobacteriaceae and related "superbugs" during gastrointestinal endoscopy.
To evaluate the risk of transmission of carbapenem-resistant Enterobacteriaceae (CRE) and their related superbugs during gastrointestinal (GI) endoscopy. Reports of outbreaks linked to GI endoscopes contaminated with different types of infectious agents, including CRE and their related superbugs, were reviewed. Published during the past 30 years, both prior to and since CRE's emergence, these reports were obtained by searching the peer-reviewed medical literature (via the United States National Library of Medicine's "MEDLINE" database); the Food and Drug Administration's Manufacturer and User Facility Device Experience database, or "MAUDE"; and the Internet (via Google's search engine). This review focused on an outbreak of CRE in 2013 following the GI endoscopic procedure known as endoscopic retrograde cholangiopancreatography, or ERCP, performed at "Hospital X" located in the suburbs of Chicago (IL; United States). Part of the largest outbreak of CRE in United States history, the infection and colonization of 10 and 28 of this hospital's patients, respectively, received considerable media attention and was also investigated by the Centers for Disease Control and Prevention (CDC), which published a report about this outbreak in Morbidity and Mortality Weekly Report (MMWR), in 2014. This report, along with the results of an independent inspection of Hospital X's infection control practices following this CRE outbreak, were also reviewed. While this article focuses primarily on the prevention of transmissions of CRE and their related superbugs in the GI endoscopic setting, some of its discussion and recommendations may also apply to other healthcare settings, to other types of flexible endoscopes, and to other types of transmissible infectious agents. This review found that GI endoscopy is an important risk factor for the transmission of CRE and their related superbugs, having been recently associated with patient morbidity and mortality following ERCP. The CDC reported in MMWR that the type of GI endoscope, known as an ERCP endoscope, that Hospital X used to perform ERCP in 2013 on the 38 patients who became infected or colonized with CRE might be particularly challenging to clean and disinfect, because of the complexity of its physical design. If performed in strict accordance with the endoscope manufacturer's labeling, supplemented as needed with professional organizations' published guidelines, however, current practices for reprocessing GI endoscopes, which include high-level disinfection, are reportedly adequate for the prevention of transmission of CRE and their related superbugs. Several recommendations are provided to prevent CRE transmissions in the healthcare setting. CRE transmissions are not limited to contaminated GI endoscopes and also have been linked to other reusable flexible endoscopic instrumentation, including bronchoscopes and cystoscopes. In conclusion, contaminated GI endoscopes, particularly those used during ERCP, have been causally linked to outbreaks of CRE and their related superbugs, with associated patient morbidity and mortality. Thorough reprocessing of these complex reusable instruments is necessary to prevent disease transmission and ensure patient safety during GI endoscopy. Enhanced training and monitoring of reprocessing staffers to verify the proper cleaning and brushing of GI endoscopes, especially the area around, behind and near the forceps elevator located at the distal end of the ERCP endoscope, are recommended. If the ERCP endoscope features a narrow and exposed channel that houses a wire connecting the GI endoscope's control head to this forceps elevator, then this channel's complete reprocessing, including its flushing with a detergent using a procedure validated for effectiveness, is also emphasized.


Comprehensive geriatric assessment in primary care: a systematic review.
Comprehensive geriatric assessment (CGA) involves the multidimensional assessment and management of an older person. It is well described in hospital and home-based settings. A novel approach could be to perform CGA within primary healthcare, the initial community located healthcare setting for patients, improving accessibility to a co-located multidisciplinary team. To appraise the evidence on CGA implemented within the primary care practice. The review followed PRISMA recommendations. Eligible studies reported CGA on persons aged ≥ 65 in a primary care practice. Studies focusing on a single condition were excluded. Searches were run in five databases; reference lists and publications were screened. Two researchers independently screened for eligibility and assessed study quality. All study outcomes were reviewed. The authors screened 9003 titles, 145 abstracts and 97 full texts. Four studies were included. Limited study bias was observed. Studies were heterogeneous in design and reported outcomes. CGAs were led by a geriatrician (n = 3) or nurse practitioner (n = 1), with varied length and extent of follow-up (12-48 months). Post-intervention hospital admission rates showed mixed results, with improved adherence to medication modifications. No improvement in survival or functional outcomes was observed. Interventions were widely accepted and potentially cost-effective. The four studies demonstrated that CGA was acceptable and provided variable outcome benefit. Further research is needed to identify the most effective strategy for implementing CGA in primary care. Particular questions include identification of patients suitable for CGA within primary care CGA, a consensus list of outcome measures, and the role of different healthcare professionals in delivering CGA.


Modulation of cell growth, p34cdc2 and cyclin A levels by SV-40 large T antigen.
Immortalization of rat lung epithelial cells by either wild-type SV-40 T antigen, a mutant form of T antigen that cannot bind pRb, or a temperature-sensitive T antigen increased by five- to 20-fold the steady state levels of p34cdc2 and cyclin A, positive regulators of progression through the cell cycle. Increased abundance of p34cdc2 was not accompanied by equivalent increases in cdc2 mRNA, indicating that increased expression of p34cdc2 is due, at least partially, to post-transcriptional mechanisms. Levels of p34cdc2 and cyclin A protein in cells immortalized with a temperature-sensitive T antigen remained elevated at the restrictive temperature unless T antigen was reduced to levels significantly below those where proliferation ceased, indicating that these two functions can be dissociated. These results show that SV-40 T antigen can dramatically enhance the expression of certain cell cycle regulatory proteins by mechanisms that are independent of pRb binding and cell growth status.