Association between sleep and severe periodontitis in a nationally representative adult US population.
Poor sleep behavior appears to have adverse effects on health by metabolic disruption and immunity suppression. Sleep disturbance is strongly associated with diabetes, cardiovascular diseases, and some cancers. This study aimed to evaluate the association between sleep duration and periodontal disease in a national US population study in a National Health and Nutrition Examination Survey (NHANES). The data were collected from individuals aged ≥30 years and included 3,624 participants in the United States NHANES 2013 to 2014. A weighted multivariable logistic regression modeling quantified the association between sleep and severe periodontal disease. We tested for diabetes as an effect modifier, adjusting for potential confounders such as smoking status, sex, age, education level, and dental visit. Individuals who sleep >7 hours/night with no trouble sleeping are 40% less likely to have severe periodontal disease (odds ratio [OR] = 0.6, P < 0.05), adjusting for age, sex, smoking status, FPL, education level, and dental visit. Additionally, diabetes was a significant positive effect modifier of the relationship between sleep and severe periodontal disease (OR = 4.8, P < 0.05). Findings of this cross-sectional representative study of an adult US population revealed a statistically significant association between sleep duration and severe periodontitis. In this study, individuals who slept >7 hours/night were less likely to exhibit severe periodontal disease. It also seems that this relationship was stronger among individuals with diabetes compared with individuals without diabetes.


Pharmacokinetic, bioavailability, and metabolism studies of lusianthridin, a dihydrophenanthrene compound, in rats by liquid chromatography/electrospray ionization tandem mass spectrometry.
Lusianthridin was reported to possess many biological properties such as anti-oxidant and anti-cancer activities. However, its metabolic profiles and pharmacokinetics in vivo remain unknown. This study was carried out to investigate the metabolic profiles and pharmacokinetics of lusianthridin in rats. The metabolic profiles were obtained by an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). A total of eighteen metabolites involved three phase I metabolites and fifteen phase II metabolites were detected and identified. The major metabolic pathways of lusianthridin were demethylation, oxidation, sulfation, glucuronidation and glutathione conjugation. In addition, a simple and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determination of lusianthridin in rat plasma. After extracted by protein precipitation, lusianthridin was quantitated in positive ion mode. The method was linear over the range of 0.5-500 ng/mL (r ≥ 0.995) with the LLOQ of 0.5 ng/mL. The intra- and inter- precision and accuracy, extraction recovery, matrix effect and stability were within the acceptable limits. The validated method was applied to the pre-clinical pharmacokinetic study of lusianthridin in rats. After oral administration, lusianthridin was quickly absorbed into plasma and reached the max concentration of 236.22 ng/mL at 22.00 min. The elimination half life of lusianthridin from plasma was approximately 83.05-104.47 min and the oral absolute bioavailability was calculated as 30.93 %.


Massive spontaneous portosystemic shunt is a solid, easily identifiable prognostic factor in patients with cirrhosis.
Spontaneous portosystemic shunts (SPSSs) are associated with complications and death in cirrhosis. We evaluated chronic portosystemic encephalopathy (CPSE) and survival in cirrhotic patients with massive (>10 mm diameter) SPSS (MSPSS). We have retrospectively compared 77 cirrhotic patients with MSPSS and 77 paired-matched patients without SPSS. More patients with MSPSS presented with CPSE (40.3% vs. 20.8%, P = 0.010) or died (33.8% vs. 18.2%, P = 0.039). Model for Endstage Liver Disease (MELD) score [hazard ratio (HR) 1.146, 95% confidence interval (CI) 1.099-1.195], follow-up (FU) ascites (HR 5.128, 95% CI 2.396-10.973) and age (HR 1.048, 95% CI 1.017-1.080) were associated with CPSE; and MELD score (HR 1.082, 95% CI 1.035-1.131), FU renal failure (HR 9.319, 95% CI 3.595-24.158), and FU ascites (HR 4.320, 95% CI 1.615-11.555) were associated with death. Liver function worsened faster in the MSPSS group. Among patients with better liver function (MELD < 11.5), MSPSS patients presented worse survival (P = 0.048, Breslow test). Comparing patients by the Child-Pugh group, we did not find differences in survival; in patients from Child-Pugh group B + C, the MSPSS group presented less time free of CPSE (P < 0.05, log-rank test). Patients with splenorenal MSPSS presented better survival (P = 0.04, log-rank test), and patients with umbilical MSPSS had shorter time free of CPSE (P < 0.016, log-rank test). MSPSS increased CPSE and death risks during long FU. Even with better liver function (MELD < 11.5), MSPSS was associated with lower survival. Splenorenal MSPSS presented better survival and the umbilical type was associated with shorter time free of CPSE.


Correlation between functional mobility and cognitive performance in older adults with cognitive impairment.
Association between cognitive impairment and gait performance occurs in mild cognitive impairment (MCI) and Alzheimer's disease (AD), particularly under "divided attention" conditions, leading to a greater risk of falls. We studied 36 controls, 42 MCI, and 26 mild AD patients, using the Timed Up-and-Go test (TUG) under four conditions: TUG single - TUG1; TUG cognitive - TUG2; TUG manual -TUG3; TUG cognitive and manual - TUG4. Cognition was assessed using the MMSE, SKT, Exit25, and TMT (A and B). We found significant correlations between cognitive scores and TUG2 [r values (MMSE: -0.383, TMT-A: 0.430, TMT-B: 0.386, Exit25: 0.455, SKT: 0.563)] and TUG4 [(MMSE: -0.398, TMT-A: 0.384, TMT-B: 0.352,Exit25: 0.466, SKT: 0.525)] in the AD group, and between all TUG modalities and SKT in MCI and AD. Our results revealed that functional mobility impairment in cognitive dual tasks correlated to cognitive decline in AD patients and to attention and memory impairment in MCI.


Compared to the amniotic membrane, Wharton's jelly may be a more suitable source of mesenchymal stem cells for cardiovascular tissue engineering and clinical regeneration.
The success of developing cardiovascular tissue engineering (CTE) grafts greatly needs a readily available cell substitute for endothelial and interstitial cells. Perinatal annexes have been proposed as a valuable source of mesenchymal stem cells (MSCs) for tissue engineering and regenerative medicine. The objective of the present study is to evaluate the potential of human Wharton's jelly MSCs (WJ-MSCs) and amniotic membrane MSCs (AM-MSCs) as a seeding cell in CTE and cardiovascular regenerative medicine. WJ-MSCs/AM-MSCs were isolated and characterized in vitro according to their morphology, proliferation, self-renewal, phenotype, and multipotency. More importantly, the characteristics of hemocompatibility, extracellular matrix deposition, and gene expression and viability of both MSCs were investigated. Fibroblast-like human WJ-MSCs and AM-MSCs were successfully isolated and positively expressed the characteristic markers CD73, CD90, and CD105 but were negative for CD34, CD45, and HLA-DR. Both MSCs shared trilineage differentiation toward the adipogenic, osteogenic, and chondrogenic lineages. The proliferative and self-renewal capacity of WJ-MSCs was significantly higher than that of AM-MSCs (P < 0.001). WJ-MSCs provided comparable properties of antiplatelet adhesion and did not activate the coagulation cascade to endothelial cells. However, aggregated platelets were visualized on the surface of AM-MSCs-derived cell sheets and the intrinsic pathway was activated. Furthermore, WJ-MSCs have superior properties of collagen deposition and higher viability than AM-MSCs during cell sheet formation. This study highlights that WJ-MSCs could act as a functional substitute of endothelial and interstitial cells, which could serve as an appealing and practical single-cell source for CTE and regenerative therapy.


The role of lymphoscintigraphy in rectal laparoscopic surgery: can the sentinel node concept be applied to rectal carcinoma?
Lymphadenectomy for rectal cancer, whether by open surgery or laparoscopy, is still a controversial subject. If we consider that approximately 20% of patients have nodal obturator metastases, then we must concede that extended lymphadenectomy is useless in the other 80% of patients. We set out to determine whether lymphoscintigraphy could show the lymphatic drainage from the cancer toward the obturator lymph nodes and thus help us to select the patients who would benefit by their removal. We also analyzed the possibility of applying the concept of the sentinel node to the treatment of rectal cancer. Among 42 people who underwent laparoscopy for rectal cancer 11 patients with TNM stages T2-T3N0M0 were studied by CT & MRI, rectal ultrasonography, and lymphoscintigraphy with a colloidal injection of human albumin labeled with 99mTc at the base of the neoplasm. Afterward, the 11 patients underwent a lymphadenectomy that extended to the obturator nodes. In two patients, lymphoscintigraphy showed lymphatic drainage toward the obturator nodes. In one case, there were metastases. Lymphoscintigraphy did not show lymphatic drainage toward the obturator nodes in any of the other patients, and there were no metastases among them. It was not possible to identify a sentinel node. Lymphoscintigraphy can be used to select patients with rectal cancer who will be helped by a lymphadenectomy extended to the obturator nodes. However, the concept of the sentinel node cannot be applied to rectal cancer.


Implementation Planning for Integrating Depression Screening in Diabetes Mellitus and HIV Clinics in Botswana.
Depression is highly prevalent and, when comorbid with other medical conditions, can worsen health outcomes. Implementing routine depression screening within medical clinics can ensure that patients receive suitable treatment and improve overall health outcomes. Unfortunately, depression screening within medical settings is rare, particularly in low- and middle-income countries. This qualitative study evaluated patient and clinician perspectives on implementing depression screening within HIV and diabetes clinics in Botswana. Seven clinicians and 23 patients within these clinics were purposively selected and interviewed using a guide informed by the Consolidated Framework for Implementation Research (CFIR) to understand barriers and facilitators to depression screening in medical clinics in Botswana. Interviews were recorded, transcribed, and analyzed using NVivo. Three general themes emerged: (1) Appropriateness and Acceptability: attitudes and beliefs from clinicians and patients about whether depression screening should occur in this setting; (2) Stigma as an important barrier: the need to address the negative associations with depression to facilitate screening; and (3) Recommendations to facilitate screening including improving knowledge and awareness about depression, offering incentives to complete the screening, providing staff training, ensuring resources for treatment, the need to preserve confidentiality, and utilizing leadership endorsement. These results offer insights into how to implement depression screening within medical clinics in Botswana. These results can help design implementation strategies to increase depression screening in these clinics, which can be tested in future studies. The online version contains supplementary material available at 10.1007/s43477-022-00062-3.


Morphine with or without Acepromazine in Horses: A Kinematic Evaluation.
The objective was to demonstrate walking locomotor pattern alterations after co-administration of acepromazine and morphine in horses. Six mature horses receiving four different treatments were used. Treatments consisted of a single dose of saline solution, 0.2 mg/kg bwt of morphine hydrochloride, 0.02 mg/kg bwt of acepromazine maleate, and a combination of 0.2 mg/kg bwt of morphine hydrochloride with 0.02 mg/kg bwt of acepromazine maleate. A three-dimensional accelerometric device was used to collect data. Walking tests were performed 10 min prior to injection, and then at 5, 10, 15, and 20 min after the injection, and then every 10 min for 3 h. Eight variables were calculated including stride kinematic, coordination, and energetic parameters; moreover ground-to-lip distance (GLD), as a tranquilization parameter, was also measured. A significant interaction was observed in all the variables studied but regularity, mediolateral power, the propulsive part of the power, and the GLD. An evident counteraction of the effects caused by both, opioids and phenothiazines, in the gait pattern was observed. The co-administration of acepromazine and morphine could allow a safe opiate administration while minimizing the possible central nervous system (CNS) excitation and reducing potential locomotor adverse effects.


Gender bias among children in India in their diet and immunisation against disease.
This paper conducts an econometric analysis of data for a sample of over 4000 children in India, between the ages of 1 and 2 years, with a view to studying two aspects of the neglect of children: their likelihood of being immunised against disease and their likelihood of receiving a nutritious diet. The starting hypothesis, consistent with an universal interest in gender issues, was that girls were more likely to be neglected than boys. The analysis confirmed this hypothesis. In respect of vaccinations, the likelihood of girls being fully vaccinated, after controlling for other variables, was 5 percentage points lower than that for boys. In respect of receiving a nutritious diet, the treatment of girls depended very much on whether or not their mothers were literate: there was no gender discrimination between children of literate mothers; on the other hand, when the mother was illiterate, girls were 5 percentage points less likely to be well-fed relative to their brothers and the presence of a literate father did little to dent this gender gap. But the analysis also pointed to a broader conclusion which was that all children in India suffered from sharper, but less publicised forms of disadvantage than that engendered solely by gender. These were the consequences which stemmed from children being born to illiterate mothers and being brought up in the more impoverished parts of India.


Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry.
The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19. The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality. Out of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82). Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.


11-Hydroxy-3,3-dimethyl-7,12-dioxo-3,4,6,6a,7,12,12a,12b-octahydrobenz[a]anthracen-1-yl acetate.
The Diels-Alder reaction between 5-hydroxy-1,4-naphthoquinone and 5,5-dimethyl-3-vinyl-1,2-cyclohexadienyl acetate by endo addition gives the title compound, C(22)H(22)O(5), in 68% yield. This racemic diastereoisomer has the opposite regiochemistry to ochromycinone analogues produced previously and may allow access to a new type of anticancer-active saquayamycin analogue.


Radiologic demonstration of multiple foci of malignancy in the esophagus.
Three patients, each with two synchronous esophageal carcinomas demonstrated radiologically, are presented. The importance of complete esophageal evaluation in patients with one obvious tumor of the esophagus is emphasized. Assessment of the full extent of disease in such cases directly affects treatment planning.


Intrinsic 2D-XY ferromagnetism in a van der Waals monolayer.
The physics and universality scaling of phase transitions in low-dimensional systems has historically been a topic of great interest. Recently, two-dimensional (2D) materials exhibiting intriguing long-range magnetic order have been in the spotlight. Although an out-of-plane anisotropy has been shown to stabilize 2D magnetic order, the demonstration of a 2D magnet with in-plane rotational symmetry has remained elusive. We constructed a nearly ideal easy-plane system, a single CrCl3 monolayer on graphene/6H-SiC(0001), and observed robust ferromagnetic ordering with critical scaling characteristic of a 2D-XY system. These observations indicate the realization of a finite-size Berezinskii-Kosterlitz-Thouless phase transition in a large-area, quasi–free-standing van der Waals monolayer magnet with an XY universality class. This offers a material platform to host 2D superfluid spin transport and topological magnetic textures.


Breast reconstruction following prophylactic mastectomy for smaller breasts: the superiorly based pectoralis fascial flap with the Becker 35 expandable implant.
Immediate reconstruction using tissue expander/implants following prophylactic mastectomy for smaller breasts is a reliable means of providing similar size, shape and symmetrical reconstructions. The superiorly based pectoralis fascial flap allows an immediate reconstruction of the inferior pole and may eliminate the need for tissue expansion. The superiorly based pectoralis fascial flap and implant was performed on 5 patients (10 breasts). The Becker 35 expandable implant was used in all cases and average size was 349 (range 290-400cc). Average age was 33 (range 21-43). The average BMI was 23 (range 20-26). One patient underwent further tissue expansion of the Becker 35 postoperatively. One patient developed a seroma in the abdominal fascial flap donor site that settled without the need for drainage. There were no other complications. The superiorly based pectoralis fascial flap provides a one-stop reconstruction of the lower pole and can eliminate the need for tissue expansion in patients with small breasts.


Associations between parental hearing impairment and children's mental health: Results from the Nord-Trøndelag Health Study.
Some previous studies indicate that parental hearing loss may have negative consequences in the parent-child relationship. However, most of these studies are qualitative or have apparent methodological shortcomings. This study is the first of its kind conducted in a large population-based sample with audiometrically measured hearing loss aimed at investigating the extent to which parental hearing loss affects adolescents' mental health. Questionnaires were administered to the adult (>19 years) and adolescent (age 13-19 years) population of Nord-Trøndelag county, Norway (1995-97), which collected information on mental and somatic health, including hearing loss. For adults participating in the study, pure tone audiometry tests were also administered. In total, 4047 fathers and 4785 mothers with self-reported hearing loss data were identified. The corresponding numbers with measured hearing loss data included 4079 fathers and 4861 mothers. The associations between the degrees of self-reported or measured parental hearing loss and the mental health of their adolescent, measured by Hopkins Symptom Check List (SCL) 5, were estimated using generalized estimating equations. After adjusting for several covariates, the mental health symptoms of adolescents were compared by parental hearing loss (i.e., with versus without hearing loss). Adolescents whose mothers had severe measured or self-reported hearing loss had significantly worse mental health than their counterparts whose mothers did not have a hearing loss. No corresponding effects were found in the adolescents whose mothers had only a slight/moderate hearing loss, neither measured nor self-reported. Paternal slight/moderate self-reported hearing loss was associated with a small significant reduction of mental health in the adolescents, although attenuated when adjusting for paternal distress. No significant effects were detected in the adolescents whose fathers had measured hearing loss. Severe maternal hearing loss is associated with significantly increased adolescent distress.


A receptor assay for somatomedin-like activity using multiplication-stimulating activity (MSA) as radioligand.
Multiplication-stimulating activity (MSA) in the medium of cultured rat liver cells was purified 120-fold by chromatography on Dowex 50W and Sephadex G 50. MSA was labelled with 125I-iodine and bound to a human placental membrane receptor. An assay for somatomedin-like receptor activity (SmLRA) in unextracted serum was based on the displacement of 125I-MSA from the placental receptor. The mean lambda (precision) was 0.063, sensitivity was less than 0.006 SmLRA units and interassay variation was 18%. The mean (+/- S.D.) SmLRA concentrations in 13 normal subjects, 7 growth hormone deficient patients and 8 patients with active acromegaly were 0.86 +/- 0.19, 0.34 +/- 0.08 and 2.34 +/- 0.82 U/ml, respectively. This assay may have potential clinical application in disorders of growth hormone secretion.


Massive tongue swelling in refractory status epilepticus treated with high-dose pentobarbital.
The potential causes of acquired macroglossia are extensive. The authors report two cases of subacute marked tongue swelling resulting in airway compromise in patients with refractory status epilepticus requiring prolonged pentobarbital coma. The hospitalization histories of the reported patients were retrospectively reviewed. The tongue swelling completely resolved in one case and significantly improved in the other after discontinuation of pentobarbital infusion or switching to phenobarbital. The authors speculate that the causes were multifarious, likely a combination of localized angioedema due to barbiturate vehicle and triggered by an initial tongue bite. Progressive tongue swelling causing airway obstruction can occur well beyond the acute phase of status epilepticus and may potentially cause problems with extubation in nontracheotomized patients.


C to T transition at the first nucleotide of codon 63 of the beta-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy.
Hemoglobin (Hb) M-Saskatoon, a beta variant of methemoglobin, is characterized by mild hemolysis. It is caused by the substitution of a histidine by a tyrosine at the 63rd amino acid residue of the beta-globin chain. Amplification and sequence analysis of genomic beta-globin DNA from an Indonesian boy diagnosed as having the more severe disease thalassemia demonstrated the presence of a C to T transition at nucleotide 473 in one of the two beta-globin genes resulting in a histidine to tyrosine substitution at 63rd residue. This amino acid change matched with that reported in Hb M-Saskatoon. This nucleotide change abolished a recognition site for the restriction endonuclease NlaIII. NlaIII digestion of the corresponding beta-globin DNA amplified from the patient's parents indicated that the mutation was inherited through from his mother. This result shows that the world-wide distribution of Hb M-Saskatoon extends to Indonesia, where it was not previously identified. Possible causes of the unusually severe symptoms observed in the case are discussed.


The application of long-read sequencing in clinical settings.
Long-read DNA sequencing technologies have been rapidly evolving in recent years, and their ability to assess large and complex regions of the genome makes them ideal for clinical applications in molecular diagnosis and therapy selection, thereby providing a valuable tool for precision medicine. In the third-generation sequencing duopoly, Oxford Nanopore Technologies and Pacific Biosciences work towards increasing the accuracy, throughput, and portability of long-read sequencing methods while trying to keep costs low. These trades have made long-read sequencing an attractive tool for use in research and clinical settings. This article provides an overview of current clinical applications and limitations of long-read sequencing and explores its potential for point-of-care testing and health care in remote settings.


Acetylcholinesterase activity in the rat brain during nephrogenic arterial hypertension and after angiotensin administration.
The activity of acetylcholinesterase was assessed in the rat brain in nephrogenic hypertension and after angiotensin administration. No significant differences were found in relation to corresponding control groups.


A systematic overview of prospective cohort studies of cardiovascular disease in sub-Saharan Africa.
Cardiovascular diseases (CVDs) are becoming increasingly significant in sub-Saharan Africa (SSA). Reliable measures of the contribution of major determinants are essential for informing health services and policy solutions. To perform a systematic review of all longitudinal studies of CVDs and related risk factors that have been conducted in SSA. We searched electronic databases from 1966 to October 2009. Published studies were retrieved from PubMed and Africa EBSCO. Reference lists of identified articles were scanned for additional publications. Any longitudinal study with data collection at baseline on major cardiovascular risk factors or CVD, including 30 or more participants, and with at least six months of follow up were included. Data were extracted on the country of study, year of inception, baseline evaluation, primary focus of the study, outcomes, and number of participants at baseline and final evaluation. Eighty-one publications relating to 41 studies from 11 SSA countries with a wide range of participants were included. Twenty-two were historical/prospective hospitalbased studies. These studies focused on risk factors, particularly diabetes mellitus and hypertension, or CVD including stroke, heart failure and rheumatic heart disease. The rate of participants followed through the whole duration of studies was 72% (64-80%), with a significant heterogeneity between studies (for heterogeneity, p < 0.001). Outcomes monitored during follow up included trajectories of risk markers and mortality. Well-designed prospective cohort studies are needed to inform and update our knowledge regarding the epidemiology CVDs and their interactions with known risk factors in the context of common infectious diseases in this region.


A review of red cell transfusion in the neurological intensive care unit.
The treatment of anemia in critically ill patients has changed significantly in the past decade with a major shift toward restrictive blood-transfusion strategy. There is a paucity of studies regarding the approach toward anemia in the neurological critical care population. Anemia is a complex problem in this group of patients because of the extreme sensitivity of brain tissue to changes in the cerebral perfusion pressure and oxygen deficit. Most of the evidence regarding management of anemia and optimal hematocrit threshold is based on animal experiments and observational studies. Recent studies have shown a mixed response in the local oxygen saturations and patient outcomes after blood transfusion in neurological critically ill patients. Although there is little reason to suspect that restrictive transfusion protocols would be detrimental, further studies are needed to determine optimal transfusion threshold in this population.


Endoscopic assessment of invasion of colorectal tumors with a new high-frequency ultrasound probe.
The present study was carried out to clarify the usefulness of and problems associated with a new ultrasound probe in the assessment of invasion of colorectal tumors. Normal colorectal wall of 23 resected specimens from colorectal cancer cases was examined in vitro with the probe. Fifty-one patients with colorectal carcinoma and 16 patients with rectal carcinoid tumor were presurgically examined using the probe via the biopsy channel of a conventional colonoscope. After endoscopic and ultrasonographic examination, 27 patients underwent endoscopic resection and 40 underwent surgical resection. The ultrasonographic findings were compared with histologic findings in all cases. Carcinomas and carcinoid tumors were visualized as an echo-poor region with the probe. The overall accuracy rate for depth of invasion was 76% (39/51) for colorectal cancer. The accuracy rates for tumors limited to the mucosa and tumors invading the submucosa were 83% and 90%, respectively; these rates were higher than those for tumors invading the muscularis propria (50%) and beyond the muscularis propria (73%). In all 16 cases of carcinoid tumor, the depth of invasion was accurately shown to be limited to the submucosa. This probe is useful to assess invasion of colorectal tumors, especially small and flat lesions limited to the mucosa or submucosa.


Modified tragus edge approach for mid-level or low condylar fractures.
The aim of this study was to evaluate and report a modified tragus edge approach (MTEA) for surgical access to mid-level or low condylar fractures. The MTEA was used on 45 patients (59 sides). All of the patients were reviewed for scarring, parotid fistula, facial nerve function, occlusion, deviation, and limitation of mouth opening (MO). Forty-one patients (64 sides) with middle or low level condylar fractures who underwent surgery by retromandibular approach during the same period were selected for comparison. In the MTEA group, scars were not obvious and there was no parotid fistula. The occlusion of four cases (8.9%) was not ideal, but returned to normal after 2 weeks of intermaxillary traction. Temporary facial nerve damage was present on two sides (3.4%). MO was not deviated in any patient, but was limited in the first 2 weeks after operation in three cases (6.7%). The risks of facial nerve dysfunction and parotid fistula were much higher in the retromandibular approach group than in the MTEA group, while the risks of malocclusion and limitation of MO were similar. MTEA is safe and has good aesthetic outcomes. MTEA represents an appropriate surgical access to mid-level and low condylar fractures.


The immortalisation of rat hepatocytes by transfection with SV40 sequences.
Abbreviations EGTA - ethylene bis(oxyethylenenitrilo)-tetraacetic acid; F12 - Ham's F12; FBS - foetal bovine serum; HBSS - Hank's balanced salt solution; HDM - hormonally defined medium; HEPES - 4-(2-hydroxyethyl)-1-piperazine ethanesulphonic acid; NBS - new born calf serum; WME - Williams' medium E.


Potent social learning and conformity shape a wild primate's foraging decisions.
Conformity to local behavioral norms reflects the pervading role of culture in human life. Laboratory experiments have begun to suggest a role for conformity in animal social learning, but evidence from the wild remains circumstantial. Here, we show experimentally that wild vervet monkeys will abandon personal foraging preferences in favor of group norms new to them. Groups first learned to avoid the bitter-tasting alternative of two foods. Presentations of these options untreated months later revealed that all new infants naïve to the foods adopted maternal preferences. Males who migrated between groups where the alternative food was eaten switched to the new local norm. Such powerful effects of social learning represent a more potent force than hitherto recognized in shaping group differences among wild animals.


A nonmathematical view of mathematical models for cancer.
A qualitative view of mathematical models for cancer is presented. The Armitage and Doll multistage and Moolgavkar two-stage models of cancer are discussed in terms of their physical models. Time-related factors for these models as well as some of their characteristics are presented. The effect of age at first exposure, duration of exposure, time since last exposure and stage of carcinogenic effect on risk are detailed.


Oral sex in an adolescent population.
The incidence of oral sex in an adolescent population is discussed. More girls have either given or received oral-genital stimulation than have had intercourse. More boys have had intercourse than have either given or received oral-genital stimulation. Oral sex is more common than intercourse for females because they are more likely to have received oral-genital stimulation than to have either had intercourse or given oral-genital stimulation. For both sexes, fellatio is less common than is either intercourse or cunnilingus. For both sexes, oral sex is considerably more frequently reported than was the case in the Kinsey surveys.


The 360 photography: a new anatomical insight of the sphenoid bone. Interest for anatomy teaching and skull base surgery.
Skull base architecture is tough to understand because of its 3D complex shape and its numerous foramen, reliefs or joints. It is especially true for the sphenoid bone whom central location hinged with most of skull base components is unique. Recently, technological progress has led to develop new pedagogical tools. This way, we bought a new real-time three-dimensional insight of the sphenoid bone that could be useful for the teacher, the student and the surgeon. High-definition photography was taken all around an isolated dry skull base bone prepared with Beauchêne's technique. Pictures were then computed to provide an overview with rotation and magnification on demand. From anterior, posterior, lateral or oblique views and from in out looks, anatomical landmarks and subtleties were described step by step. Thus, the sella turcica, the optic canal, the superior orbital fissure, the sphenoid sinus, the vidian canal, pterygoid plates and all foramen were clearly placed relative to the others at each face of the sphenoid bone. In addition to be the first report of the 360 Photography tool, perspectives are promising as the development of a real-time interactive tridimensional space featuring the sphenoid bone. It allows to turn around the sphenoid bone and to better understand its own special shape, numerous foramen, neurovascular contents and anatomical relationships. This new technological tool may further apply for surgical planning and mostly for strengthening a basic anatomical knowledge firstly introduced.


Coalescing expansile skeletal disease: Delineation of an extraordinary osteopathy involving the IFITM5 mutation of osteogenesis imperfecta type V.
In 2003, we briefly reported the remarkable osteopathy of a 12-year-old boy who at age two months began fracturing his limbs with subsequent hyperplastic callus formation and expansion and fusion of appendicular bones. By age ten years he had coalesced his lumbosacral spine, pelvis, femurs, and leg and foot bones as a single structure. Computed tomography of expanded bone revealed a thin cortical shell, diminished irregular trabeculae, and cystic areas. Histopathology featured foci of woven bone, densely packed osteocytes, cartilage, fibrovascular tissue, and massive fat deposition in the marrow space lacking hematogenous precursor cells. Bone turnover markers indicated accelerated remodeling and the few radiographically assessable appendicular bones improved during brief adherence to alendronate therapy. Following puberty, serum multiplex biomarker profiling confirmed accelerated bone turnover. At age 23 years, macrospecimens from leg amputation revealed ossification along capsular tissue together with hyaline cartilage degeneration. Concurrently, the life-long course of this same disorder was delineated in an unrelated woman until her death at age 51 years. Both patients demonstrated the radiographic hallmarks and harbored the heterozygous point mutation (c.-14C>T) in the 5'-UTR of IFITM5 associated with osteogenesis imperfecta type V (OI-V). Herein, we detail the clinical, radiological, histopathological, biochemical, and molecular findings and discuss the etiology and pathogenesis of this extraordinary osteopathy that we call coalescing expansile skeletal disease.


Decreased expression of fos-related antigens (FRAs) in the hypothalamic dopaminergic neurons after immunoneutralization of endogenous prolactin.
In our previous studies we found that administration of exogenous prolactin increased dopamine turnover in the terminal areas of the hypothalamic dopaminergic neurons controlling prolactin secretion from pituitary lactotrophs. In this study we investigated the effect of immunoneutralization of endogenous prolactin on the expression of FRAs in the tuberoinfundibular dopaminergic (TIDA), tuberohypophysial dopaminergic (THDA), and periventricular hypothalamic dopaminergic (PHDA) subpopulations of the hypothalamic dopaminergic neurons. Female rats were ovariectomized on d 0 of the experiment. At 1000 h of d 10, all animals were injected with 20 microg of 17-beta-estradiol sc to induce a proestrous-like surge of prolactin at 1700 h the next day. At 1000 h on d 11, half of the animals were injected with 200 microL of rabbit anti-rat prolactin antiserum ip, while the controls received normal rabbit serum. Groups of animals were sacrificed for immunocytochemistry in 2 h intervals between 1300 and 2100 h. Double-label immunocytochemistry for FRAs and tyrosine hydroxylase (TH) was performed and the results are presented as percentage of TH-immunoreactive neurons expressing FRAs. In the control animals, expression of FRAs decreased at 1500 h, gradually increased by 1900 h, but was lower than the basal levels by 2100 h. Expression of FRAs was significantly lower at 1900 h in the PHDA, THDA and TIDA neurons of prolactin antiserum treated rats than in the controls. These results indicate that elimination of endogenous prolactin from the circulation lowers the activity and/or prevents the reactivation of neuroendocrine dopaminergic neurons at the beginning of the dark phase.


Time-dependency of serum carbamazepine concentration.
Serum CBZ concentration was determined by gas liquid chromatographic method in 14 epileptic patients (32 samples) treated initially with CBZ alone, and the following results were obtained: 1. The relationship between serum CBZ concentration and CBZ dose was expressed by a regression line that sloped sharply upwards at first: high serum concentration was obtained from small dose up to the end of three weeks after initiation of CBZ administration. After the 3rd--4th treatment week, regression coefficient was reduced by half, and the regression line had a gentler slope. 2. As the treatment was continued longer, serum CBZ concentration and serum concentration/dose ratio became lower. The relationship between duration of CBZ treatment and serum concentration/dose ratio was expressed by a regression curve representing a quadratic function with negative coefficient, the ratio being high in early stage of the treatment. This regression curve shows that the ratio reached its maximum value at the 10.5 days after initiation of the treatment. The ratio was stabilized at a low level about 3--4 weeks after that. 3. From the results, serum CBZ concentration was confirmed to be more dependent on duration of the treatment than on dose. This was inferred, on the basis of documentary research, to be attributable to the autoinduction of CBZ metabolism, the inference of which seemed to be supported by the results of measurement of time-course change in serum concentration in five cases of the present series. The results in one of the said five cases suggest that serum CBZ concentration varies greatly within 12 hr. 4. On the basis of these results, it is proposed that spontaneous decrease in serum CBZ concentration must be countered not merely by increase in CBZ dose, but by increase in the number of dosages/day for suppression of excessive diurnal change in serum concentration as well.


Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis.
Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures. We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses. This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.


Comparison of phenotypic and genotypic frequency of phosphine resistance in select field populations of Tribolium castaneum from India.
Tribolium castaneum causes substantial damage to stored grains, leading to economic losses. The present study evaluates phosphine resistance in adult and larval stages of T. castaneum from north and northeast India, where continuous and long-term phosphine use in large-scale storage conditions intensifies resistance, posing risks to grain quality, safety, and industry profitability. This study utilized T. castaneum bioassays and CAPS markers restriction digestion methodology to assess resistance. The phenotypic results indicated a lower LC50 value in larvae compared to adults, while the resistance ratio remained consistent across both stages. Similarly, the genotypic analysis revealed comparable resistance levels regardless of the developmental stage. We categorized the freshly collected populations based on resistance ratios, with Shillong showing weak resistance, Delhi and Sonipat displaying moderate resistance, and Karnal, Hapur, Moga, and Patiala exhibiting strong resistance to phosphine. Further validation by accessing findings and exploring the relationship between phenotypic and genotypic variations using Principal Component Analysis (PCA). This comprehensive study enhances our understanding of T. castaneum resistance levels, providing valuable insights for the development of targeted pest management strategies. This study provides insights into the current phenotypic and genotypic resistance levels of T. castaneum in North and North East India. Understanding this is crucial for developing effective pest management strategies and future research on biological and physiological aspects of phosphine resistance in insects, enabling the formulation of effective management practices. Addressing phosphine resistance is vital for sustainable pest management and the long-term viability of the agricultural and food industries.


Early outcomes of laparoscopic sleeve gastrectomy in a multiethnic Asian cohort.
Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric operation worldwide. To report early outcomes of patients with LSG performed. University hospital and a restructured hospital, Singapore. Data of patients who underwent LSG as a primary procedure from 2008 to 2013 were analyzed for change in body mass index (BMI), percentage of weight loss (%WL), and percentage of excess weight loss (%EWL). The remission of obesity-related co-morbidities after LSG was analyzed. Logistic regression analyses were performed to determine predictive factors for perioperative complication and suboptimal EWL. Two hundred operations were performed on a cohort that consisted of 74 Chinese, 57 Malay, and 52 Indian patients and 17 patients from other ethnic groups. Mean preoperative weight and BMI were 118.1±26.8 kg and 43.0±8.0 kg/m(2), respectively. Mean follow-up duration was 16.7±9.4 months. At 6, 12, 24 and 36 months, the percentage of patients followed-up were 79.5%, 75.7%, 50.0%, and 50.0%, and the mean %EWL were 51.2%, 61.2%, 60.9%, and 51.0%, respectively. Postoperative complications occurred in 9 patients (4.5%), 5 of whom (2.5%) required reoperation. There was no mortality in our series. Remission of type 2 diabetes mellitus (T2DM) was significantly associated with achieving>50% EWL (P = .009). Patients>50 years of age and higher preoperative BMI were significant factors for failure to achieve>50% EWL at 1 year after LSG. LSG is a safe and effective operation for achieving significant weight loss and improvement of co-morbidities in multiethnic Asian population. Adequate EWL is important to achieve remission of T2DM. Older patients and higher preoperative BMI are predictive factors for suboptimal EWL.


Racing justice: Mass incarceration and perceptions of courts.
This article examines how the emergence of mass incarceration in the United States affected public perceptions of its judicial institutions. Analyses of General Social Survey data collected between 1974 and 2018 indicate that the rising incarceration rate was associated with distinctive changes to Blacks' and Whites' views of courts. As the incarceration rate increased, Blacks' confidence in courts and the legal system fell while Whites' confidence grew. The rising incarceration rate was also associated with a growing Black-White fissure in confidence in the Supreme Court. Finally, although Blacks and Whites each became more likely to believe that courts are too punitive as incarceration increased, the change in these attitudes was twice as large among Blacks than Whites. Overall these results suggest that mass incarceration contributed to a rift in Blacks' and Whites' support for judicial institutions. This article also underscores the importance of macro-level institutional contexts for understanding individuals' perceptions of institutional authorities.


[Evolution of man's concept of death over time. II].
Durkheim's sociocultural theories about suicide form the basis for an analysis of current sociocultural conditions as possible causal elements for the alleged recent increase in adolescent suicides.


Distribution of DYZ2 repetitive sequences on the human Y chromosome.
The distribution of the 2000 copies of the Y-specific repetitive family DYZ2 is controversial since previous reports have mapped these sequences to different sites of the Yqh region. In this work, we have performed non-radioactive in situ hybridization of a cloned DYZ2 fragment at higher stringency conditions on 5-aza-cytidine-enlarged Y chromosomes; the results suggest a non-uniform distribution of these sequences, which are preferentially located at the proximal and distal parts of Yqh, including the C+/Q- heterochromatin at the boundary with the euchromatic region.


Intracerebroventricularly infused angiotensin II or III do not alter voluntary alcohol intake in rats.
Subcutaneous injections of angiotensin (ANG) II or III in the periphery reduce alcohol intake and raise water intake. These peptides do not cross the blood-brain barrier and cannot reach the angiotensin receptor-rich sites surrounding the lateral and third ventricles. To examine the effect on alcohol intake of ANG II and III at these ventricular sites, groups of rats were first trained to drink alcohol using a limited access procedure, then surgically prepared with chronic indwelling lateral or third ventricular cannulae, and then reoffered daily 40-min access to alcohol. Neither ANG II (25-200 ng) nor ANG III (25-100 ng) had any effect on alcohol consumption at either of the two ventricular sites. Water consumption was significantly enhanced by both peptides at both sites and could be attenuated by prior treatment with the ANG II antagonist Sar1Thr8-ANG II. The SC administration of ANG II was able to produce a significant reduction in alcohol drinking. These findings demonstrate that ICV administered ANG II or ANG III do not modulate alcohol drinking and that changes in alcohol intake do not result from the thirst promoted by ANG II. Sites in the periphery may be more involved in the interaction between angiotensin and alcohol consumption.


Epicardial Termination of Left Atrial Appendage Atrial Tachycardia.
This case report describes a third successful attempt to ablate a focal atrial tachycardia originating from the left atrial appendage in a highly symptomatic 49-year-old woman using a combined endocardial-epicardial approach, which could be taken into consideration as a safe and effective alternative method for treating similar arrhythmias originating from complex sites.


In vivo formation of a carcinogenic substance from diethyl pyrocarbonate in the presence of ammonia.
Mice of different strains have been treated repeatedly with diethyl pyrocarbonate (DEPC) and/or ammonia by gastric tube. In adult mice treated with DEPC plus ammonia, pulmonary tumours developed. However, DEPC or ammonia alone proved not to have any carcinogenic effect. When DEPC administration was followed by ammonia treatment more pulmonary tumours developed than in the case of ammonia-DEPC sequence. The shorter the time interval between DEPC and ammonia administrations the higher the number of lung tumours observed. Pulmonary tumours could not be observed in the offspring of pregnant mice treated with DEPC and ammonia or in suckling mice whose mother was treated with DEPC and ammonia. In gastric juice a new substance is formed from DEPC in the presence of ammonia. This new substance was very similar or identical to urethane according to the thin layer chromatographic investigation.


Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia--a report of two cases.
Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).


The effect of GIH and Boots secretin and cholecystokinin on duodenal ulcers in the rat.
The effects of two commercially available preparations of secretin and cholecystokinin have been studied on experimental duodenal ulcers in the rat. Pentagastrin and carbachol infused subcutaneously over 24 hours produced a 100% incidence of duodenal ulcers. A dose-related inhibition of these ulcers was found using secretin obtained from the Gastrointestinal Hormone Laboratory, Stockholm (GIH). Boots secretin had no such inhibitory action and may even have aggravated the duodenal ulcerogenesis. Similar results were obtained with both GIH cholecystokinin and Boots pancreozymin.


Protist Evolution: Stealing Genes to Gut It Out.
The amount and evolutionary impact of horizontal gene transfer in eukaryotes remain contentious issues. A new phylogenomic study suggests that gene transfer from prokaryotes has contributed significantly to the adaptation and metabolic evolution of Blastocystis, the most widespread human gut eukaryotic parasite.


Halogenoalkyl isocyanates as bifunctional reagents in an Aza-Wittig/heterocyclization reaction on the solid phase: efficient entry into new tetracyclic benzimidazole systems.
An efficient one-pot procedure for the solid-phase synthesis of new tetracyclic 1,3,5-triazino[1,2-a]benzimidazolium derivatives starting from resin-bound benzimidazoles is described. The synthetic strategy involves an unprecedented one-pot Aza-Wittig/heterocyclization/substitution reaction sequence using halogenoalkyl isocyanates. The structure of the tetracyclic ring system was determined by two-dimensional NMR experiments and X-ray analysis.


Cyclooxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and cardiovascular risk.
Cyclooxygenase-2 (cox-2) inhibitors, also known as coxibs, were introduced with the promise that they would provide pain relief similar to that of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) but would be better tolerated with lower risk of gastrointestinal (GI) side effects. Although coxibs were associated with lower GI risk, experimental and observational data raised the specter of increased cardiovascular risk associated with this class of drugs. This article describes the pharmacologic and biologic basis of cardiovascular risk associated with coxibs, summarizes the evidence for cardiovascular risk associated with cox-2 inhibitors, and weighs the risks and potential benefits of pain management with these agents.


Identification of three class II antigens, DR7, MB2, and MT3, from a homozygous human cell line.
The class II antigens from a homozygous DR7 human B cell line were isolated by immunoprecipitation with human alloantisera or monoclonal antibodies. Three class II light chains and three class II heavy chains were identified. The heavy and light chain subunits of the DR7 antigen were distinct from those of the MB2 antigen as assessed by two-dimensional gel electrophoresis. A third light chain in addition to the DR7 and MB2 subunits was precipitated by some alloantisera containing MT3 antibodies. The monoclonal antibodies examined immunoprecipitated one or more of the three class II antigens. The MB2 antigen appeared to be the same as the major antigen recognized by L227 and the DS7 antigen precipitated by SG171.


The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats exhibiting addiction-like behavior.
Medication development for cocaine-addicted patients is difficult, and many promising preclinical candidates have failed in clinical trials. One reason for the difficulty in translating preclinical findings to the human condition is that drug testing is typically conducted in behavioral procedures in which animals do not show addiction-like traits. Recently, a DSM-IV-based animal model has been developed that allows studying the transition to an addiction-like behavior. Changes in synaptic plasticity are involved in the transition to cocaine addiction. In particular, it has been shown that metabotropic glutamate receptor 2/3 (mGluR2/3)-mediated long-term depression is suppressed in the prelimbic cortex in addict-like rats. We therefore hypothesized that cocaine-seeking in addict-like rats could be treated with an mGluR2/3 agonist. Indeed, addict-like rats that were treated systemically with the mGluR2/3 agonist LY379268 (0, 0.3, and 3 mg/kg) showed a pronounced reduction in cue-induced reinstatement of cocaine-seeking. In an attempt to dissect the role played by mGluR2 and mGluR3 in cue-induced reinstatement, we analyzed the mRNA expression patterns in several relevant brain areas but did not find any significant differences between cocaine addict-like and non-addict-like rats, suggesting that the behavioral differences observed are due to translational rather than transcriptional regulation. Another possibility to study the contributions of mGluR2 and mGluR3 in mediating addictive-like behavior is the use of knockout models. Because mGluR2 knockouts cannot be used in operant procedures due to motoric impairment, we only tested mGluR3 knockouts. These mice did not differ from controls in reinstatement, suggesting that mGluR2 receptors are critical in mediating addictive-like behavior.


Silicone gel including antimicrobial agent.
Silicone gel sheets containing Ofloxacin (OFLX), that provide a continual drug delivery system from a wound dressing to the wound so as to prevent infection and to promote healing, are described. It was found that silicone gel sheets without added medication did not inhibit microbial growth but that gel sheets containing 0.02% and 0.2% of OFLX had a positive antimicrobial effect against Staphylococcus aureus and Pseudomonas aeruginosa in a dose-dependent fashion in vitro. Further, this antimicrobial efficacy was greatly increased in a silicone gel sheet that contained 0.02% of OFLX and an additional 10% of silicone oil. In animal experiments, a silicone gel sheet containing OFLX prevented microbiol growth and promoted rapid epithelialisation in wounds to which Staphylococcus aureus had been applied, whereas wounds covered only with OpSite all resulted in continued infection.


Effectiveness of laser and topical tranexamic acid combination therapy in melasma: An updated systematic review and meta-analysis of randomized controlled trials.
Melasma is a chronic relapsing skin condition. Laser therapy is a new advancement in treatment. Whether the topical application of tranexamic acid (TXA) increases the efficacy of laser therapy in melasma is still under debate. With recent studies yielding different results, it was imperative to compile all the available literature systematically. This meta-analysis investigates the effectiveness of a combination therapy of laser plus TXA acid for treating melasma. PubMed/MEDLINE, Cochrane Central, Google Scholar, Scopus, and the International Clinical Trials registry were systematically searched for article retrieval. Screening per PRISMA guidelines was undertaken by two independent reviewers using the Covidance database. Melasma area of severity index (MASI)/modified MASI was used as the clinical improvement outcomes. A total of nine studies that described the combined use of topical tranexamic acid with laser therapy were included for meta-analysis. These studies employed various types of lasers along with topical TXA. The results showed that the combination of both laser therapy and topical TXA significantly decreased the MASI score (P < 0.0001). Subgroup analyses revealed that fractional CO2 laser among the laser types and monthly laser plus twice daily topical TXA were most effective in decreasing the MASI/mMASI score. The meta-analysis found that combining topical tranexamic acid and laser therapy is an effective and safer treatment option for treatment-resistant melasma. Furthermore, monthly fractional CO2 laser and daily application of topical tranexamic acid showed high effectiveness and safety.


Arrhythmias, catecholamines and electrolytes.
The prognosis in patients with heart failure secondary to left ventricular dysfunction is poor. Although survival can be related to the extent of cardiac functional impairment, many patients die suddenly rather than in refractory heart failure. Ambulatory electrocardiography has revealed a high prevalence of simple and complex ventricular arrhythmias in these patients, which was the most important predictor of subsequent mortality in our patients. Factors predisposing to arrhythmias are many, but increased catecholamines and electrolyte abnormalities are among the more obvious. In patients who have undergone treatment for congestive heart failure, serum and total body potassium are reduced, and this is closely and inversely related to the state of activation of the renin-angiotensin system. Renin and noradrenaline are also closely and directly correlated, while both are inversely related to the arterial pressure. Treatment with angiotensin-converting enzyme inhibitors tends to reverse these neuroendocrine and electrolyte abnormalities and reduces the frequency of ventricular arrhythmias. Whether this will have a favorable impact on mortality, and, in particular, on sudden death, remains to be seen.


A hospital clinic-based survey on traditional Chinese medicine usage among chronic hepatitis B patients.
To survey the pattern of traditional Chinese medicine usage among chronic hepatitis B patients. Self-administered questionnaire survey. Hepatitis clinic at a university hospital in Hong Kong. Proportion of chronic hepatitis B patients who have ever used traditional Chinese medicine for the treatment of chronic hepatitis B and factors associated with the use. Three hundred and sixty-two patients completed the survey (response rate 93%). One hundred and sixteen (32%) patients reported history of traditional Chinese medicine usage. One hundred and five (91%) patients felt that Chinese medicine had few or no side effects. Most (81%) patients did not inform their physicians on Chinese medicine usage. On multivariate analysis, recent travel to Mainland China, perceived active hepatitis and family members with chronic hepatitis B were independent factors associated with the use of Chinese medicine. Chronic hepatitis B patients commonly use traditional Chinese medicine. As patients seldom inform the physicians about the use of Chinese medicine, doctors should explicitly enquire about this because of potential therapeutic implications.


Cascaded two-photon nonlinearity in a one-dimensional waveguide with multiple two-level emitters.
We propose and theoretically investigate a model to realize cascaded optical nonlinearity with few atoms and photons in one-dimension (1D). The optical nonlinearity in our system is mediated by resonant interactions of photons with two-level emitters, such as atoms or quantum dots in a 1D photonic waveguide. Multi-photon transmission in the waveguide is nonreciprocal when the emitters have different transition energies. Our theory provides a clear physical understanding of the origin of nonreciprocity in the presence of cascaded nonlinearity. We show how various two-photon nonlinear effects including spatial attraction and repulsion between photons, background fluorescence can be tuned by changing the number of emitters and the coupling between emitters (controlled by the separation).


Tumor necrosis factor-alpha is a marker of familial combined hyperlipidemia, independently of metabolic syndrome.
It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.


Triple inhibitor titrations support the functionality of the dimeric character of mitochondrial ubiquinol-cytochrome c oxidoreductase.
The ubiquinol-2 or duroquinol oxidoreductase activity of mitochondrial ubiquinol-cytochrome c oxidoreductase was titrated with combinations of antimycin, myxothiazol and N,N'-dicyclohexylcarbodiimide (DCCD). A statistical model has been developed that can predict the activity of the complex treated with all possible combinations of these inhibitors. On the basis of the measured titration curves the model had to accommodate interaction between the two promoters of the complex. The titrations confirm that treatment with DCCD results in the modification of a certain site in one of the two promoters of the bc1 dimer, thereby blocking one antimycin A binding site without inhibiting electron transfer. Modification of both antimycin A binding sites of the dimer is apparently required for inhibition of electron transfer through the complex, just as modification of both myxothiazol-binding sites is required for full inhibition. The conclusion can be drawn that mitochondrial ubiquinol-cytochrome c oxidoreductase is a functional dimer, consisting of electrically interacting protomers.


Clinical trials of long-term RF local hyperthermia for advanced gastric cancer.
The effect of local hyperthermotherapy (HT) using 13.56-MHz radiofrequency (RF) capacitive heating was evaluated in 25 patients with unresectable or recurrent gastric cancer. HT was carried out once to 3 times a week for a duration of one hour at each session. Patients who underwent RF-HT frequently showed maintenance of performance status, symptomatic improvement and a reduction in tumor size. Moreover, the survival time of 9 patients who had numerous metastases to the distant peritoneum was significantly high (p less than 0.01), compared with 42 historical control patients who also had massive peritoneal dissemination, but had not received HT. The results of this study therefore indicate RF-HT to be a favorable modality in the palliative treatment of patients with far-advanced gastric cancer.


Genotype distribution in chronic hepatitis C patients in Greece.
Hepatitis C is a major public health problem. HCV infection contributes to progressive liver disease, cirrhosis, and hepatocellular carcinoma. HCV has high genetic heterogeneity and is classified into various genotypes and subtypes. Regional differences exist in their distribution. The aim of this study was to investigate the relative frequency of HCV genotypes in Greek patients with chronic infection. We evaluated 82 patients with chronic HCV infection, both males and females, belonging to different risk groups. We performed viral load measurement and HCV genotyping in all specimens. HCV genotype 3 was the most prevalent (41.5%) followed by genotype 1 (34.1%), 2 (12.2%), 4 (10.9%), and 5 (1.2%). Genotype 6 was not detected in any patient. Most prevalent subtypes were 3a (32.9%), 1b (26.8%), and 2a (6.1%). Fourteen subjects revealed mixed infections within types. There were no cases with mixed infections across types. Our data indicate that genotypes 3a and 1b are the most prevalent in Greek patients. Genotype 3a is predominant in younger patients and also in male patients. Moreover, HCV genotype distribution is in continuous temporal change in Greece.


Wear and damage in retrieved humeral inlays of reverse total shoulder arthroplasty-where, how much, and why?
Polyethylene (PE) wear and material degradation have been reported as complications in reverse total shoulder replacements (rTSAs). In this regard, scapular notching is associated with more clinical complications. Therefore, the purposes of the study were to quantify the linear and volumetric wear, as a measure for the amount of removed material, and to qualitatively assess the PE damage modes to describe the material degradation in retrieved rTSA humeral PE inlays that contribute to failure of shoulder replacements. Furthermore, this study aimed to evaluate the effect of scapular notching on PE wear and rim damage of the humeral components. The total study population of 39 humeral inlays contains 2 cohorts that were used for the damage mode analysis and for the wear analysis, respectively. The extent and presence of wear damage modes in 5 defined zones were assessed by a grading system for all PE joint replacements. For quantitative wear analysis the most frequent design (n = 17) was chosen. Using a coordinate-measuring machine and postprocessing software, volumetric wear measurements for the retrieved humeral PE inlays were undertaken. Furthermore, prerevision radiographs were analyzed for scapular notching. Finally, retrieval findings were correlated with clinical and radiographic data to consider the effect of notching and to identify risk of failures for these prostheses. Damage on the rim of the humeral PE inlays was more frequent and severe than on the intended articulation surface. Irrespective of the damage mode, the inferior rim zone sustained the greatest amount of wear damage followed by the posterior zone. Burnishing, scratching, pitting, and embedded particles are most likely to occur in the articular surface area, whereas surface deformation, abrasion, delamination and gross material degradation are predominantly present in the inferior and posterior rim zones. The retrieved inlays exhibited a mean volumetric wear rate of 296.9 mm³/yr ± 87.0 mm³/yr. However, if the notched and non-notched components were compared, a significant higher volumetric wear rate (296.5 ± 106.1 mm³/yr) was found for the notched components compared to the non-notched group (65.7 ± 7.4 mm³/yr). Generally, there was a significantly greater incidence of damage and greater amount of wear if scapular notching occurred. The notched components showed a 5-fold increase in PE wear rate. Therefore, scapular notching has a strong effect on PE damage and wear. If scapular notching can be clinically avoided, the PE wear performance is in a similar magnitude as found for hip and knee replacements.


Classification of age groups and task conditions provides additional evidence for differences in electrophysiological correlates of inhibitory control across the lifespan.
The aim of this study was to extend previous findings on selective attention over a lifetime using machine learning procedures. By decoding group membership and stimulus type, we aimed to study differences in the neural representation of inhibitory control across age groups at a single-trial level. We re-analyzed data from 211 subjects from six age groups between 8 and 83 years of age. Based on single-trial EEG recordings during a flanker task, we used support vector machines to predict the age group as well as to determine the presented stimulus type (i.e., congruent, or incongruent stimulus). The classification of group membership was highly above chance level (accuracy: 55%, chance level: 17%). Early EEG responses were found to play an important role, and a grouped pattern of classification performance emerged corresponding to age structure. There was a clear cluster of individuals after retirement, i.e., misclassifications mostly occurred within this cluster. The stimulus type could be classified above chance level in ~ 95% of subjects. We identified time windows relevant for classification performance that are discussed in the context of early visual attention and conflict processing. In children and older adults, a high variability and latency of these time windows were found. We were able to demonstrate differences in neuronal dynamics at the level of individual trials. Our analysis was sensitive to mapping gross changes, e.g., at retirement age, and to differentiating components of visual attention across age groups, adding value for the diagnosis of cognitive status across the lifespan. Overall, the results highlight the use of machine learning in the study of brain activity over a lifetime.


Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Action of the hormone on cytoplasmic processing of ribonucleic acid after reserpine treatment.
Treatment of perfused rabbit heart with reserpine causes a decrease of incorporation of labelled precursors into RNA species of subcellular fractions and polyamines. Ornithine decarboxylase, S-adenosylmethionine decarboxylase and cytoplasmic Mn2+-stimulated polyadenylate polymerase activities are not modified. Addition of noradrenaline to reserpine-treated perfused hearts enhances, compared with the control, the incorporation of precursor into RNA in all subcellular fractions other than the nuclear one, restores incorporation of labelled putrescine into polyamines, enhances ornithine decarboxylase and S-adenosylmethionine decarboxylase activities and causes a 12-fold increase in cytoplasmic Mn2+-dependent polyadenylate polymerase activity. After treatment with noradrenaline the increase in radioactivity was found solely in AMP after hydrolysis of microsomal RNA to nucleoside monophosphates.


A comparative magnetic resonance spectroscopy study of GABA+ and glutamate referenced to creatine and phosphocreatine in the left dorsolateral prefrontal cortex of perimenopausal women and women of reproductive age.
The perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible for this increased risk of depression remain to be elucidated. Postmortem and magnetic resonance spectroscopy (MRS) studies have revealed decreased gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the dorsolateral prefrontal cortex (DLPFC) of MD patients. The objective of this study was to compare LDLPFC GABA+ and Glu ratios (referenced to creatine and phosphocreatine) in healthy reproductive-aged (RD) and perimenopausal (PM) women. Eighteen healthy PM and 20 RD women were included in the study. Our dependent variables, LDLPFC Glu and GABA+ ratios which include homocarnosine and macromolecules, were measured via MRS, using a 3 Tesla magnet. Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles. Mean LDLPFC GABA+ and Glu ratios were not statistically different between the PM group and RD group (PM mean = 0.10 ± 0.06, RD mean = 0.11 ± 0.04, t = -0.383, df = 36, d = -0.13, p = 0.70) (PM mean = 0.56 ± 0.06, RD mean = 0.57 ± 0.05, t = -0.794, df = 36, d = -0.26, p = 0.43), respectively. The perimenopause demarcates the end of the reproductive life. Unsurprisingly PM women were older than RD women (PM women: 48.8 ± 3.55 years, range 41-53 years old; RD women: 31.5 ± 9.66 years, range 18-47 years old) (p < 0.001). This inherent entanglement of group and age is a limitation of our study. Contrary to our previous findings of decreased GABA+ and Glu in the medial prefrontal cortex in perimenopausal women, the perimenopause is not associated with decreased GABA+ or Glu ratios in the LDLPFC. This suggests that brain areas playing a role in MD display different sensitivity to the female hormones fluctuations associated with perimenopause.


The tactile sensors of the gut.
In a recent study, Treichel, Finholm et al. showed that the mechanoreceptor Piezo2 enables enteroendocrine cells in the intestinal epithelium to sense luminal contents. Through neuroepithelial signaling, these cells modulate intestinal motility and transit of digestive products.


Manganese-52m for direct application: a new 52Fe/52mMn generator based on a hydroxamate resin.
A new generator system has been developed using the 52Fe/52mMn parent-daughter pair. A polymeric hydroxamate resin is used for the fixation of 52Fe, and the short-lived positron-emitter 52mMn is eluted in physiological saline. Preliminary animal studies in rats gave similar results with respect to biodistribution as are obtained for [54Mn] manganous chloride.


[Sentinel lymph node detection and intra-operational diagnosis in patients with early stage cervical cancer].
To study the effective method for rapid detection of sentinel lymph nodes in patients with early stage cervical cancer and clinical value thereof. Thirty female patients with early stage cervical cancer, 14 at FIGO stage IB1 and 16 at stage IIA, underwent injection of 99mTc-labelled sulfur colloid 0.4 mci/0.4 ml at the positions of 3, 6, 9, and 12 o'clock of the cervix 5 h or 18 h before operation, and injection of 1 ml of methylene blue at the same cervical positions as mentioned above after the abdomen was opened. The blue-stained lymph nodes or the lymph nodes directed by the blue-stained lymph vessels were identified as SLNs: gamma-detector was used to position the hot nodes. The SLNs were resected and then radical hysterectomy and pelvic lymphadenectomy were performed. SLN frozen section and imprint cytology were conducted during the operation, the results were compared with that of HE staining SLN were detected successfully in 29 of the 30 patients with a detection rate of 96.7%. Routine HE staining indicated pelvic lymph node metastasis in 9 patients. The SLN was positive in 8 of the 29 patients, negative in 20 patients, and false negative in 1 patient. The sensitivity, accuracy, and false-negative rates of SLN detection were 88.9%, 96.6%, and 11.1% respectively. The sensitivity, specificity, accuracy, and positive and negative predictive rates were 92.3%, 100%, 98.9%, 100%, and 98.8% for frozen section, and 92.3%, 97.6%, 96.8%, 85.7%, and 98.8% for imprint cytology respectively. Frozen section and imprint cytology may be effective rapid methods to diagnose SLN metastasis during operation. SLN detection can predict pelvic lymph node metastasis in cervical cancer.


Methadone dose and treatment outcome.
Consensus on the optimal dosing of methadone in the treatment of opioid dependence has not yet been achieved, with some programs committed to low dose regimens. This paper presents outcome results for 95 opioid abusers who remained in treatment through a stable dosing period in a double-blind fixed dose clinical trial comparing the relative efficacies of 50 (n = 44) and 20 mg (n = 34) of methadone to methadone-free treatment (n = 17). All patients showed improvements over time on measures of psychosocial functioning and psychological symptoms, emphasizing the important role of non-pharmacologic factors in methadone treatment. Furthermore, orderly dose effect relationships were seen, with patients receiving 50 mg of methadone having significantly lower rates of opioid positive urines (36% vs. 60-73%), and self-reporting a lower frequency of heroin use (3 days vs. 11-12 days per month). These results illustrate the dose-related efficacy of methadone in decreasing illicit opioid use and improving drug-related behavior.


Substrate specificity for interfacial catalysis by phospholipase A2 in the scooting mode.
Action of pig pancreatic phospholipase A2 on vesicles and micelles of homologous anionic phospholipids is examined in the absence of additives. As shown elsewhere (Jain et al. (1986) Biochim. Biophys. Acta 860, 435-447), hydrolysis of anionic vesicles occurs by interfacial catalysis in the scooting mode, i.e., the catalytic turnover is fast relative to the off-rate of the enzyme from the interface. When the rate of intervesicle exchange of the enzyme is negligibly slow, it hydrolyses only the substrate molecules in the outer monolayer of the vesicle to which it is bound. Interfacial catalysis in the scooting mode with a high processivity occurs on vesicles of anionic phospholipids, and under these conditions the dynamics and order of the substrate in the interface influences the catalytic turnover only moderately, i.e., about 2- to 10-fold. Similarly, anomalous kinetic effects of the thermotropic gel-fluid phase transition or of a change in the general disorder of the bilayer organization (fluidity) has a minor effect on the kinetics of hydrolysis in the scooting mode. Similarly, higher unsaturation and shorter acyl chains in the substrate modestly increase the rate of catalytic turnover by the low-calcium form of the enzyme without noticeably influencing the affinity of the enzyme for the interface. On the other hand, perturbation of the charge distribution in the substrate interface can shift the proportion of the bound enzyme by several orders of magnitude. For example, the membrane perturbing amphiphiles (e.g., mepacrine, indomethacin, compound 48/80, aristolochic acid, local anesthetics, and the products of hydrolysis) do not influence the catalytic turnover of the bound enzyme but the proportion of the bound enzyme. Short-chain anionic phospholipids are readily hydrolyzed by phospholipase A2. Now no anomalous increase in the rate of hydrolysis is observed at the critical micelle as is the case with the zwitterionic analogs. This is because with anionic (but not with zwitterionic) substrates the enzyme forms an aggregated complex below the cmc of the monomer. The stability of these micellar complexes does not appear to change noticeably with the acyl chain length of the monomers. These observations show that the factors regulating the quality of interface substantially influence the binding of the enzyme, but not the catalytic turnover in the interface.


Improving Sexual Assault and Sexual Harassment Prevention from the Bottom-up: a Pilot of Getting To Outcomes in the US Military.
While the Department of Defense (DoD) has given increased attention and priority to preventing sexual assault and sexual harassment (SA/SH), it remains a problem. To build its prevention capacity, DoD piloted Getting To Outcomes® (GTO®) from 2019 to 2022 at 10 military installations. GTO is an evidence-based planning and implementation support that has been used in many civilian contexts but has only recently been adapted for military SA/SH. The purpose of this study was to describe GTO use, identify its benefits and challenges, and discuss lessons the GTO effort yielded for prevention more broadly using a framework of organizational and program-level capacities needed for successful prevention in the military context, called the Prevention Evaluation Framework (PEF). GTO was piloted with 10 military installations ("sites") representing all Military Services, plus the Coast Guard and National Guard. GTO is comprised of a written guide, training, and ongoing coaching. The pilot's goal was for each site to use GTO to implement a SA/SH prevention program twice. Participants from each site were interviewed and data was collected on GTO steps completed, whether GTO spurred new evaluation activities and collaborations, and the degree of leadership support for GTO. Most sites completed all GTO steps at least once. Interviews showed that DoD participants believe GTO improved prevention understanding, planning, and evaluation capacity; strengthened confidence in chosen programs; and helped sites tailor programs to the military context. Barriers were the complexity of GTO, DoD personnel turnover, and the disruption that the COVID pandemic caused in sexual assault prevention program delivery. Many respondents were unsure if they would continue all of GTO after the coaching ended, but many believed they would continue at least some parts. According to the PEF, the GTO pilot revealed several additional prevention system gaps (e.g., need for leadership support) and changes needed to GTO (e.g., stronger leader and champion engagement), to support quality prevention. The military and other large organizations will need to focus on these issues to ensure prevention implementation and evaluation are conducted with quality.


Purification and characterization of cytochrome c oxidase from rat liver mitochondria.
Cytochrome c oxidase has been purified from rat liver mitochondria using affinity chromatography. The preparation contains 10.5 to 13.4 nmol of heme a + a3 per mg of protein and migrates as a single band during polyacrylamide gel electrophoresis under nondissociating conditions. It has a heme a/a3 ratio of 1.12 and is free of cytochromes b, c, and c1 as well as the enzymes, NADH dehydrogenase, succinic dehydrogenase, coenzyme Q-cytochrome c reductase, and ATPase. The enzyme preparation consists of six polypeptides having apparent Mr of 66,000, 39,000, 23,000, 14,000, 12,500 and 10,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The peptide composition is similar to those found for cytochrome c oxidases from other systems. The enzymatic activity of the purified enzyme is completely inhibited by carbon monoxide or cyanide, partially inhibited by Triton X-100 and dramatically enhanced by Tween 80 or phospholipids.


Components of the plasminogen activator system and their complexes in renal cell and bladder cancer: comparison between normal and matched cancerous tissues.
To analyse and compare the concentration of plasminogen activator (PA), urokinase-type PA (uPA), tissue-type PA (tPA), PA inhibitor (PAI)-1 and PAI-2, and the complexes uPA-PAI-1 and tPA-PAI-1 and calculated uPA and tPA uncomplexed with PAI-1 ('free') in urothelial cell carcinoma and matched benign urothelium, and in renal cell carcinoma (RCC) and matched benign renal tissue. Tissue samples were obtained during cystectomy (33 patients) and nephrectomy (55), and specific enzyme-linked immunosorbent assays were used to assess the PA components in extracts of these tissues. Tissue levels of uPA-PAI-1 and tPA-PAI-1, but also PAI-1 itself, were greater in tumorous bladder and kidney tissue than in matched normal tissue (by 1.5-7.8 times). Free tPA was clearly lower in tumour tissue (by 0-0.12-fold). In bladder cancer, but not in RCC, levels of uPA (15.8-fold) and free uPA (16.4-fold) were greater in tumour tissue. Free uPA levels were less in RCC (0.41-fold). For both normal bladder and kidney tissue, there was no clear correlation between uPA-PAI-1 complex and either component. However, the formation of tPA-PAI-1 complexes in normal bladder and kidney tissue was primarily determined by PAI-1. Interestingly, in tumour tissues there was a strong, significant correlation between complex levels and both components. RCC and bladder cancer show distinct profiles of components of the PA system. This study provides a basis for further studies into both the (patho)physiological role of the PA system in these tumours, and into a possible relation with tumour progression and prognosis, and as target for therapy.


Cranial nerve injury during carotid arterial reconstruction.
In a series of 109 carotid arterial reconstructions cranial nerve injury was observed in 14 of 102 patients. Ipsilateral peripheral hypoglossal nerve injury occurred in nine patients with carotid occlusive disease. The marginal mandibular nerve was injured in three patients and recurrent laryngeal nerve dysfunction was noted in four patients. Two cranial nerves were injured in two patients. Full recovery of hypoglossal dysfunction was seen within 2-52 weeks (average 20 weeks). The nerves are injured by retraction to clear the operative field or by postoperative haematoma. Risk factors include crossing of the hypoglossal nerve close to the carotid bifurcation or procedures requiring long arteriotomy or skeletonization of the internal carotid artery. Unilateral cranial nerve injury is usually mild but will require delay of controlateral carotid reconstruction to avoid severe bilateral cranial nerve palsy.


Combining Community-Based Participatory Research (CBPR) with a Random-Sample Survey to Assess Smoking Prevalence in an Under-Served Community.
The authors would like to thank Laura McClure for her help with the manuscript submission, the Liberty City Community Health Advisory Board for its collaboration on this study, as well as the survey interviewers, and the survey participants. Underserved communities might lag behind Healthy People 2010 objectives of smoking reduction because of smoking behavior disparities. This possibility was investigated through a random-sample survey conducted in a disenfranchised community in Miami-Dade County, Florida, using a Community-Based Participatory Research (CBPR) framework. The survey was triggered by our finding that this community had higher than expected incidence of tobacco-associated cancers. Survey methods, resulting from a dialog between the Community Advisory Board and academic researchers, included: (a) surveying adult residents of a public housing complex located within the community; (b) probability sampling; (c) face-to-face interviews administered by trained community residents. 250 households were sampled from 750 addresses provided by the county Public Housing Agency. The completed surveys were reviewed by the academic team, yielding 204 questionnaires for the current analysis. Of the 204 respondents, 38% were current smokers. They estimated the percentages of smokers in their household and among their five best friends at 33% and 42%, respectively, and among adults and youth in the community at 72% and 53%, respectively. A mix of state-of-art methodology with CBPR principles is seldom encountered in the current literature. It allowed the research team to find a high smoking prevalence in an underserved community, twice the statewide and nationwide estimates. Similar or higher levels of smoking were perceived in respondent's entourage. Such disparity in smoking behavior, unlikely to result from self-selection bias because of our rigorous methodology, calls for community-specific tobacco control efforts commensurate to the magnitude of the problem.


Rational Computational Design of Systems Exhibiting Strong Halogen Bonding Involving Fluorine in Bicyclic Diamine Derivatives.
Perhaps the most controversial and rare aspect of the halogen bonding interaction is the potential of fluorine in compounds to serve as a halogen bond donor. In this note, we provide clear and convincing examples of hypothetical molecules in which fluorine is strongly halogen bonding in a metastable state. Of particular note is a polycyclic system inspired by Selectfluor, which has been controversially proposed to engage in halogen bonding.


Ranking the most influential predictors of CT-based radiomics feature values in metastatic lung adenocarcinoma.
To investigate which acquisition, post-processing, tumor, and patient characteristics contribute the most to the value of radiomics features (RFs) in lung adenocarcinoma in order to better understand and order the potential sources of bias in radiomics studies in a multivariate setting. This single-center retrospective study included all consecutive patients with newly-diagnosed lung adenocarcinoma treated between December 2016 and September 2018 who had pre-treatment contrast-enhanced CT-scan showing ≥ 2 target lesions per response evaluation criteria in solid tumors (RECIST) v1.1. All measurable lesions were manually segmented; 49 RFs were extracted using LIFEx v7.0.0. Afterwards, we reverted the usual radiomics approach (i.e., predicting a clinical outcome base on multiple RFs). To do so, for each RF, random forests and linear regression algorithms were trained using cross-validation to predict the RF value depending on the following variables: patient, mutational status, phase of CT-scan acquisition, discretization (binsize), lesion location, lesion volume, and best response obtained during the first line of treatment (partial response per RECIST vs other). The most important contributors to the value of reproducible RFs (intra-class correlation coefficient > 0.80) according to the best random forests model (selected via R-squared) were ranked. 101 patients (median age: 62.3) were included, with a median of 5 target lesions per patient (range: 2-10) providing 466 segmented lesions. Twenty-nine RFs were reproducible. The most important predictors of the reproducible RFs values were, in order: tumor volume, binsize, tumor location, CT-scan phase, KRAS mutation, and treatment response (average importance: 61.7%, 57.4%, 8.1%, 3.3%, 3%, and 2.7%, respectively). The treatment response and KRAS and EGFR/ROS1/ALK mutational status remained independently correlated with the RF value for 64.3%, 32.1%, and 50% reproducible RFs, respectively. Tumor volume, location, acquisition and post-processing parameters should systematically be incorporated in radiomics-based modeling; however, most reproducible RFs do have significant relationships with mutational status and treatment response.


Succinic semialdehyde dehydrogenase deficiency in children and adults.
Succinic semialdehyde dehydrogenase deficiency is a rare disorder of the degradation pathway of gamma-aminobutyric acid. The disorder is detected when 4-hydroxybutyric aciduria is present on urine organic acid analysis, and is subsequently confirmed by enzyme measurement on leucocytes. The disorder has been identified in approximately 350 individuals worldwide. We review the clinical features in 60 patients. The most common characteristics are developmental delay maximally involving expressive language, hypotonia, mental retardation, ataxia, and behavioral problems. Seizures occur in approximately half of patients, and include tonic-clonic, absence, and myoclonic seizures, including status epilepticus. Electroencephalographic findings are background slowing and generalized and focal epileptiform discharges. Magnetic resonance imaging typically reveals increased T2-weighted signal of the globus pallidus bilaterally, with variable involvement of white matter and the cerebellar dentate nucleus. Preliminary human cerebrospinal fluid measurements are consistent with neurometabolic aberrations documented in the murine animal model, with elevations in gamma-aminobutyric acid, gamma-hydroxybutyrate, and homocarnosine, and low glutamine. Succinic semialdehyde dehydrogenase deficiency may be an underrecognized neurometabolic disorder with a nonspecific and wide phenotypic spectrum, and carries implications for a comprehensive fundamental understanding of interrelations between multiple neurotransmitter systems.


Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.
Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a highly conserved protein tyrosine phosphatase (PTP), which is encoded by PTPN11 and is indispensable during embryonic development. Mutations in PTPN11 in human patients cause aberrant signaling of SHP2, resulting in multiple rare hereditary diseases, including Noonan Syndrome (NS), Noonan Syndrome with Multiple Lentigines (NSML), Juvenile Myelomonocytic Leukemia (JMML) and Metachondromatosis (MC). Somatic mutations in PTPN11 have been found to cause cancer. Here, we focus on the role of SHP2 variants in rare diseases and advances in the understanding of its pathogenesis using model systems.


NMR studies on Na+ transport in Synechococcus PCC 6311.
The freshwater cyanobacterium Synechococcus PCC 6311 is able to adapt to grow after sudden exposure to salt (NaCl) stress. We have investigated the mechanism of Na+ transport in these cells during adaptation to high salinity. Na+ influx under dark aerobic conditions occurred independently of delta pH or delta psi across the cytoplasmic membrane, ATPase activity, and respiratory electron transport. These findings are consistent with the existence of Na+/monovalent anion cotransport or simultaneous Na+/H(+)+anion/OH- exchange. Na+ influx was dependent on Cl-, Br-, NO3-, or NO2-. No Na+ uptake occurred after addition of NaI, NaHCO3, or Na2SO4. Na+ extrusion was absolutely dependent on delta pH and on an ATPase activity and/or on respiratory electron transport. This indicates that Na+ extrusion via Na+/H+ exchange is driven by primary H+ pumps in the cytoplasmic membrane. Cells grown for 4 days in 0.5 M NaCl medium, "salt-grown cells," differ from control cells by a lower vmax of Na+ influx and by lower steady-state ratios of [Na+]in/[Na+]out. These results indicate that cells grown in high-salt medium increase their capacity to extrude Na+. During salt adaptation Na+ extrusion driven by respiratory electron transport increased from about 15 to 50%.