Translating research into improved outcomes in comprehensive cancer control.
A key question in moving comprehensive cancer control (CCC) plans into action is, to what extent should the knowledge gained from investments in cancer prevention and control research influence the actions taken by states, tribes, and territories during implementation? Underlying this 'should' is the assumption that evidence-based approaches (i.e., a public health or clinical intervention or policy that has resulted in improved outcomes when scientifically tested), when implemented in a real-world setting, will increase the likelihood of improved outcomes. This article elucidates the barriers and opportunities for integrating science with practice across the cancer control continuum. However, given the scope of CCC and the substantial investment in generating new knowledge through science, it is difficult for any one agency, on its own, to make a sufficient investment to ensure new knowledge is translated and implemented at a national, state, or local level. Thus, if greater demand for evidence-based interventions and increased resources for adopting them are going to support the dissemination initiatives described herein, new interagency partnerships must be developed to ensure that sufficient means are dedicated to integrating science with service. Furthermore, for these collaborations to increase both in size and in frequency, agency leaders must clearly articulate their support for these collaborative initiatives and explicitly recognize those collaborative efforts that are successful. In this way, the whole (in this context, comprehensive cancer control) can become greater than the sum of its parts.


The significance and importance of prenatal diagnosis of fetal cardiac malformations by Doppler echocardiography.
Pulsed Doppler echocardiography is an excellent technique for cardiac diagnosis and assessment of cardiac performance in combination with M-mode and two-dimensional echocardiography. Its exact role in fetal cardiac diagnosis has not been established. We examined 67 high-risk fetuses for cardiac malformations and found cardiac abnormalities or malfunction in 15. In four fetuses pulsed Doppler echocardiography played a primary or a definitive diagnostic role: One fetus had a complete atrioventricular canal, another lacked the pulmonary valve, the third had transposition of the great vessels without ventricular septal defect, and the fourth had high cardiac output failure caused by placental chorioangioma. Pulsed Doppler echocardiography is an integral part of the ultrasonic cardiac examination in high-risk fetuses and should be used in combination with two-dimensional and M-mode echocardiography. It has an important place in the diagnosis of high-risk fetuses and may have a primary role in the diagnosis of fetuses when ultrasound resolution is poor, where cardiac circulatory hemodynamics are essential for diagnosis, and in complicated cardiac malformations in which a comprehensive and accurate diagnosis can be achieved only with pulsed Doppler echocardiography.


Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle.
Erythromycin, one of the macrolide antibiotics, and its derivatives had been found to mimic actions of exogenous motilin, a gastrointestinal peptide hormone. We found that some of the macrolide compounds inhibited the specific binding of 125I-motilin to rabbit duodenum muscle at 15 C in a dose-dependent fashion. The inhibitory activity of several macrolides examined did not relate to their antibacterial activity but to their motilin-like activity. A 50% inhibition by EM536, a non-antibacterial erythromycin derivative with the highest motilin-like activity, was obtained at 3-40 nM and little higher than that of non-radioactive motilin (5-6 nM) under the present conditions. The results suggest that erythromycin and its derivatives mimic physiological actions of motilin by acting as agonists for a motilin receptor.


Effect of operative time on complications associated with free flap reconstruction of the head and neck.
To evaluate whether prolonged operative time is negatively associated with post-operative complications and length of stay in patients undergoing microvascular free flap reconstruction for complex head and neck defects. 342 consecutive patients undergoing microvascular reconstruction for head and neck defects between 2017-2019 at a single institution were evaluated. Operative outcomes and operative time were compared whilst controlling for patient and treatment related factors. Mean operative time was 551 min and length of stay was 16.2 days. An 11% increase in the risk of a post-operative complication was observed for every additional hour of operative time (OR 1.11, 95% CI 1.03-1.21, p = 0.011) after adjusting for patient and treatment factors. A cut-off of 9 h yielded a 92% increase in complications on either side of this (OR 1.92, 95% CI 1.18-3.13, p = 0.009). Increased operative time was also associated with increased length of stay and return to theatres, but not medical complications. Prolonged operative time is significantly associated with increased surgical complications, length of stay and return to theatres when performing microvascular reconstructive surgery for head and neck defects.


The Effect of a Community-Based Exercise Program on Inflammation, Metabolic Risk, and Fitness Levels Among Persons Living with HIV/AIDS.
The human immunodeficiency virus (HIV) pandemic remains a top national health priority. Chronic inflammation may be a critical component in the disease course of HIV as C-reactive protein (CRP) is elevated and associated with increased mortality. This study examined the effect of 3 months of combined aerobic and resistance exercise training among a diverse cohort of HIV-infected men and women. The fixed effect of time for CRP was found to be non-significant (F[1,57.3] = 1.7, p = 0.19). There was a significant fixed effect for time for upper body (F[1,51.6] = 18.1, p < 0.05) and lower body strength (F[1,48.0] = 15.7, p < 0.05) and significant declines in diastolic blood pressure (p = 0.002) and waist circumference (p = 0.027). Though levels of CRP were not impacted after 3 months training, participants demonstrated a significant increase in muscular strength as well as beneficial changes in metabolic risk factors. Future studies should focus on determining the optimal exercise intervention length and mode to reduce inflammation among individuals living with HIV.


Infection-related hospitalizations over 30 years of follow-up in patients starting renal replacement therapy at pediatric age.
Pediatric renal replacement therapy (RRT) patients surviving long-term are at a much higher risk of mortality compared with the age-matched general population. Recently, we demonstrated a transition from cardiovascular disease to infection as the main cause of death in a long-term follow-up study of pediatric RRT. Here, we explore the burden of infections requiring hospitalization over 30 years of follow-up on RRT. The cohort comprised all 234 Dutch patients on RRT under 15 years of age between 1972 and 1992. We analyzed infection-related hospitalizations during the period 1980–2010. We evaluated the Hospital Admission Rate (HAR) per patient-years (py) and infectious over noninfectious HAR ratio (HARR). The HAR decreased significantly over time for all patients. The rate of hemodialysis-related infections decreased between 1980 and 1999, but stabilized during 2000–2010, whereas peritoneal dialysis-related infections decreased progressively. Transplantation-related infections did not change, except for urinary tract infections (UTIs), which increased significantly from 3.3/100 py [95%CI 3.2–3.4] in 1980–1989 to 4.4/100 py [4.2–4.5] in 2000–2010 (p <0.001). The contribution of infection to HAR increased significantly in transplanted patients (HARR: 1980–1989: 0.25 [0.2–0.3]; 2000–2010: 1.0 [0.79–1.27], p <0.001). Our findings indicate a relative increase in infections requiring hospitalization over time in patients starting RRT during the pediatric age, especially severe UTIs in transplantation. More attention paid to urological abnormalities in cases of recurrent UTI and tailored adjustment of immunosuppression may reduce risk in these patients.


Evaluation of the concurrent use of potassium-influencing drugs as risk factors for the development of hyperkalemia.
Hyperkalemia is a potentially dangerous electrolyte abnormality with a reported incidence of 1-10 % in hospitals. Patients are especially at risk of developing this complication if they use a combination of potassium supplements and potassium sparing diuretics or renin-angiotensin-aldosterone-system (RAAS) inhibitors. Previous studies on the occurrence of hyperkalemia in patients who use multiple potassium influencing drugs simultaneously were either small in sample size or did not investigate the full range of drugs involved. To assess the prevalence of hyperkalemia and to identify risk factors for its development in hospitalised patients using potassium supplements, potassium-sparing diuretics and/or RAAS-inhibitors concurrently. The study was conducted at the Onze Lieve Vrouwe Hospital in Amsterdam, The Netherlands from January 2009 to May 2010. A retrospective, nested case-control study included hospitalised patients who used a combination of potassium-influencing drugs. Cases were patients with serum potassium ≥ 5.5 mmol/l, controls were patients with normal serum potassium levels. Cases and controls were included in a ratio of 1:2. The following known risk factors associated with hyperkalemia were recorded and statistically analyzed: diabetes mellitus, congestive heart failure, decreased renal function, advanced age, gender and use of heparin, digoxin, non-steroidal anti-inflammatory drugs, beta-blockers, calcineurin antagonists and trimethoprim. Identify risk factors for the development of hyperkalemia as a result of the concurrent use of potassium supplements, RAAS inhibitors and/or potassium-sparing diuretics. Of 774 patients included in this study, 52 patients developed hyperkalemia; a prevalence of 6.7 %. The only risk factor found to be significantly associated with hyperkalemia was lowered renal function, expressed as estimated glomerular filtration rate (eGFR) <50 ml/min (adjusted OR 5.08; 95 % CI 2.46-10.48). None of the other tested risk factors was identified as significant. This study showed that decreased renal function (eGFR <50 ml/min) was associated with a fivefold increased risk for hyperkalemia in patients using potassium-influencing drugs. While previous studies showed that hyperkalemia substantially increases below a threshold of eGFR <30 or 40 ml/min, we observed a lower threshold of eGFR <50 ml/min. It is therefore recommended that physicians should be particularly alert while monitoring the use of potassium-influencing drugs in patients with decreased renal function.


The aetiology and clinical significance of the sinusoidal fetal heart-rate pattern; two case reports.
Two cases are presented in which sinusoidal heart-rate (SHR) patterns were recorded antenatally. In the first case the pattern was associated with severe maternal exertion and prolonged exposure to freezing temperatures. The pattern returned to normal within an hour of maternal recovery. The second case was associated with fetal death due to high-output cardiac failure associated with a large liver haemangioma. A hypothesis is proposed to link the aetiology for this heart-rate pattern which would explain these, and previously reported cases.


The effects of packaging type and storage temperature on some of UHT milk quality indexes.
The objective of the present study was to illustrate the changes in physicochemical properties in ultra-high temperature (UHT) milk packed into a pouch and Tetra Brik during storage. UHT milk samples were kept at 5 and 25 °C for 3 months and regularly analyzed monthly. During storage, significant increases (p < 0.05) in titratable acidity (TA), water-soluble nitrogen (WSN), and non-protein nitrogen (NPN) when UHT milk was packed into pouch versus Tetra Brik and stored at 25 versus 5 °C. Neither type of packaging nor storage temperature affect pH values during storage. Spore-forming bacterial (SFB) count was always higher in UHT milk packed into pouch versus Tetra Brik. Refrigerated storage kept UHT milk without detectable SFB compared to UHT milk held at 25 °C. Pouch packages were responsible for the migration of phthalate derivatives [dimethyl phthalate "DMP", diethyl phthalate "DEP", dibutyl phthalate "DBP", and di-(2-Ethylhexyl) phthalate "DEHP"] into milk with significantly greater levels than milk filled into Tetra Brik. The total sensory scores were decreased significantly during storage, which was more pronounced in UHT milk filled into pouch versus Tetra Brik or stored at 25 °C versus 5 °C. It is concluded that UHT milk filled into Tetra Brik stored at 5 and 25 °C is better in terms of quality and safety indexes than such filled into a pouch.


Postoperative complications influence prognosis and recurrence patterns in periampullary cancer.
The present study was performed to elucidate the influence of postoperative complications on the prognosis and recurrence patterns of periampullary cancer after pancreaticoduodenectomy (PD). Clinical data were reviewed from 200 consecutive patients who had periampullary cancer and underwent PD between October 2003 and July 2010, and survival outcomes and recurrence patterns were analyzed. Postoperative complications were classified according to a modification of Clavien's classification. Overall, 86 major complications of grade II or higher occurred in 71 patients. The patients were classified into two groups according to the presence of postoperative complications of grade II or higher: group Cx-, absence of complications (n = 129); and group Cx+, presence of complications (n = 71). There were no differences in gender, mean age, tumor node metastasis stage, biliary drainage, type of resection, and radicality between the two groups (P > 0.05). The 3-year overall and disease-free survival rates of the group Cx+ patients (31.0 and 22.3 %, respectively) were significantly lower than those of the group Cx- patients (49.0 and 40.0 %; P = 0.003 and 0.002, respectively). The multivariate analysis showed that postoperative complications (P = 0.001; RR = 1.887; 95 % confidence interval [CI] 1.278-2.785), a T stage of T3 or T4 (P = 0.001; RR = 2.503; 95 % CI 1.441-4.346), positive node metastasis (P = 0.001; RR = 2.093; 95 % CI, 1.378-3.179), R1 or R2 resection (P = 0.023; RR = 1.863; 95 % CI 1.090-3.187), and angiolymphatic invasion (P = 0.013; RR = 1.676; 95 % CI 1.117-2.513) were independent prognostic factors for disease-free survival. Regarding recurrence patterns, group Cx+ patients exhibited more distant recurrences than did group Cx- patients (P = 0.025). Postoperative complications affect prognosis and recurrence patterns in patients with periampullary cancer after PD.


Low-frequency positive-pressure ventilation with extracorporeal carbon dioxide removal.
Successful use of a new technique, low-frequency positive-pressure ventilation with extracorporeal CO2 removal (LFPPV-ECCR) is presented. The association of fulminant respiratory failure with CNS hemangioblastoma, described in the present patient, has been reported only once before, in 1928.


Epilepsy classification and factors associated with control in Saudi adult patients.
There is insufficient information on the epilepsies in Saudi Arabia. The objectives were to classify the patients according to seizure types and epilepsies as well as to determine the factors associated with control. In a hospital-based study, clinical information, electroencephalographic and neuroimaging findings were utilized to classify the cases into seizure types and epilepsies according to ILAE criteria and to determine the factors statistically associated with control. In the study there were 826 patients (454 males and 372 females; mean age = 28.7 years; >80% below 30 years at onset). The seizure types were: generalized tonic-clonic (43.8%), partial seizure secondarily generalized (41.9%), myoclonic (8.4%), simple partial (1.3%), complex partial (1.3%) and absence (0.4%). About 15% of the classifiable epilepsies were symptomatic. Most symptomatic epilepsies occurred in people over the age of 50 years. One-year remission rate was 80% and the factors associated with control were: compliance, monotherapy, therapeutic drug level and seizure type. The results showed that epilepsy predominantly affected young adults and confirmed the association of partial epilepsy with clinical and CT abnormalities. The 1-year remission rate was comparable with reports from other studies as well as the factors associated with control in our patients.


Bioavailability and release of nonextractable (bound) residues of chiral cycloxaprid using geophagous earthworm Metaphire guillelmi in rice paddy soil.
The widespread adoption of neonicotinoids has led to a move away from integrated pest management (IPM) and caused adverse effects on non-target invertebrate species. Due to their living in close contact with and consuming large amounts of soil, earthworms are a model organism used to study bioaccumulation. We investigated the bioaccumulation and release of bound, or non-extractable, residues (BRs) of (14)C labeled racemic cycloxaprid (CYC) and its individual enantiomers by the geophagous earthworm Metaphire guillelmi. In a previous work, the fraction of BRs of (14)C-CYC individual enantiomers reached up to 70-85% of the initially spiked radioactivity after 100 d of treatment. The bulk volume of the soil was then diluted by a factor of 15 with fresh soil. Here we showed that after earthworms lived in the soil-bound residues for 28 d, 11-25% of the previously bound radioactivity in soil was extractable by solvent, mineralized to CO2, and accumulated in earthworm tissues. While earthworms were exposed to (14)C-CYC a two-compartment accumulation model could explain the bio-accumulation as individual enantiomers. At the end of the experiment, the biota-sediment accumulation factors were between 0.59 and 0.82, which suggested CYC immobilization in the soil resulted in its bioavailability being reduced which enhanced its degradation. Additionally, the elimination of CYC individual enantiomers from M. guillelmi was fitted to an availability-adjusted decay model with a half-life of 9 d. Stereoselective release or bioavailability between CYC enantiomers was not observed. These results provide the important data about the release of BRs of CYC and potential transfer in the food chain to support the long-term environmental risk assessment of neonicotinoids.


Children who experience their first fracture at a young age have high rates of fracture.
Rate of fracture was examined according to age at first fracture in 313 New Zealand children (145 girls, 168 boys) under l3 years of age (95.4% of a consecutive series of children treated at one hospital for a recent confirmed fracture at any site). In their lifetimes they had experienced 468 separate fracture events, over half (54.7%) occurring in the 32.3% of children breaking bones on more than one occasion. Children experiencing a first fracture before 4 years of age had 36.7 (95%CI 30.7-44.1) fractures per l00 years of exposure: this was a significantly higher rate than that of children experiencing their first fracture later in life. Thus, using the <4.0 year age group as a reference, we found that rate ratios (adjusted for gender) for groups that had suffered the first fracture at later ages were: first fracture between 4.0 and 6.99 years, 0.77 (95%CI 0.58-1.03); first fracture between 7.0 and 9.99 years, 0.63 (95%CI 0.42-0.94); first fracture between 10.0 and 12.99 years, 0.48 (95% CI 0.32-0.72). Asthma was over-represented (31% seen, 25% expected), and a high proportion of the sample (32.9%) used corticosteroid medications; however, neither characteristic affected age at first fracture. In contrast, the large number (n= 42) of youngsters (13.4% of the sample) reporting adverse reactions to milk were younger at first fracture than children without reactions to milk (P<0.05). We conclude that children experiencing their first fracture at a young age have high rates of fracture and should be targeted for advice to improve their bone strength.


Pulmonary edema due to Plasmodium vivax malaria in an American missionary.
Pulmonary edema is a recognized complication of Plasmodium falciparum malaria but is uncommon with Plasmodium vivax infection. We report the case of a non-immune adult with imported P. vivax malaria who developed pulmonary edema during treatment. The case was further complicated by a recurrent malaria episode after failure of acute quinine and doxycycline treatment followed by terminal primaquine therapy. Prompt recognition and appropriate management of pulmonary edema is needed for optimal outcomes of P. vivax infection, as well as awareness of the potential failure of terminal therapy for liver hypnozoites.


Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains.
Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn(2+)-binding domain (residues 642-1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn(2+)-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein-protein interactions.


Differentiating bipolar disorder-not otherwise specified and severe mood dysregulation.
Bipolar disorder-not otherwise specified (BP-NOS) and severe mood dysregulation (SMD) are severe mood disorders that were defined to address questions about the diagnosis of bipolar disorder (BD) in youth. SMD and BP-NOS are distinct phenotypes that differ in clinical presentation and longitudinal course. The purpose of this review is to inform clinicians about the clinical features of the two phenotypes and about the research literature distinguishing them. A literature review was performed on SMD as studied in the National Institute of Mental Health Intramural Research Program and on BP-NOS in youth. For BP-NOS, the phenotype defined in the Course of Bipolar Youth study is the focus, because this has received the most study. SMD is characterized by impairing, chronic irritability without distinct manic episodes. Most commonly, BP-NOS is characterized by manic, mixed, or hypomanic episodes that are too short to meet the DSM-IV-TR duration criterion. Research provides strong, albeit suggestive, evidence that SMD is not a form of BD; the most convincing evidence are longitudinal data indicating that youth with SMD are not at high risk to develop BD as they age. The BP-NOS phenotype appears to be on a diagnostic continuum with BD types I and II. Subjects with BP-NOS and those with BD type I have similar symptom and family history profiles, and youth with BP-NOS are at high risk to develop BD as they age. Currently, little research guides treatment for either phenotype. Pressing research needs include identifying effective treatments for these phenotypes, ascertaining biomarkers that predict conversion from BP-NOS to BD, elucidating associations between SMD and other disorders, and defining the neural circuitry mediating each condition.


Site-directed mutagenesis and feedback-resistant N-acetyl-L-glutamate kinase (NAGK) increase Corynebacterium crenatum L-arginine production.
N-acetyl-L-glutamate kinase (EC 184.108.40.206) is first committed in the specific L-arginine pathway of Corynebacterium sp. A limited increase of L-arginine production for the argB overexpression in the engineering C. creantum SYPA-CCB strain indicated that L-arginine feedback inhibition plays an influence on the L-arginine production. In this study, we have performed site-directed mutagenesis of the key enzyme (NAGK) and the three mutations (E19R, H26E and H268D) exhibited the increase of I0.5R efficiently. Thereby, the multi-mutated NAGKM3 (including E19R/H26E/H268D) was generated and its I0.5R of L-arginine of the mutant was increased remarkably, whereas the NAGK enzyme activities did not declined. To get a feedback-resistant and robust L-arginine producer, the engineered strains SYPA-CCBM3 were constructed. Introducing the argBM3 gene enabled the NAGK enzyme activity insensitive to the intracellular arginine concentrations resulted in an enhanced arginine biosynthesis flux and decreased formation of by-products. The L-arginine synthesis was largely enhanced due to the overexpression of the argBM3, which is resistant to feedback resistant by L-arginine. Thus L-arginine production could reach 45.6 g/l, about 41.7% higher compared with the initial strain. This is an example of up-modulation of the flux through the L-arginine metabolic pathway by deregulating the key enzyme of the pathway.


Evaluation of the eruption of permanent teeth and their association with malocclusion.
This study was done to determine the timing of eruption of permanent teeth by sex and the number of permanent teeth erupted at different ages and to assess its association with malocclusion. The sample for this study consisted of 633 healthy subjects (317 boys and 316 girls) aged between 5.0 and 15.0 years. The subjects were divided into subgroups considering an age interval of 1 year. The mean eruption times were lower for girls compared with boys except for the maxillary and mandibular second premolars and second molars, which were found to erupt earlier in boys. All the permanent mandibular teeth, except the second premolars, tended to erupt earlier than their maxillary antagonists in both sexes. The sequence of eruption differs between girls and boys in the maxillary canine and maxillary second premolars. In Class III malocclusion, all the permanent mandibular teeth erupt earlier than their maxillary antagonists. In the entire sample, the correlation between the number of erupted teeth and age was strong (p < .05), but the differences between sexes were not significant. It is important to know the normal eruption time of permanent teeth in the population due to diagnosis and better treatment planning in pediatric dentistry and orthodontics.


Low molecular weight immunosuppressors secreted by adult Nematospiroides dubius.
Adult Nematospiroides dubius excretory-secretory products (ES) were collected from worms cultured in vitro, separated by sodium dodecyl sulphate--polyacrylamide gel electrophoresis (SDS-PAGE) into four fractions (FI-IV), electroeluted and assessed for their ability to inhibit the proliferation of mouse lymphocytes stimulated by mitogens in vitro. The proliferation of mitogen- and ES-stimulated mouse spleen lymphocytes from normal and infected mice was inhibited by low mol. wt ES F-IV (less than 26,000).


Polymorphisms of P-selectin glycoprotein ligand-1 are associated with neutrophil-platelet adhesion and with ischaemic cerebrovascular disease.
P-selectin glycoprotein ligand (PSGL-1) shares common features with platelet glycoprotein Ibalpha. A recently described polymorphism in this receptor that results in a variable number of tandem repeats (VNTR) sequence present either 16, 15 or 14 times (alleles A, B or C) could, similar to GPIbalpha, be functionally relevant. The allelic frequency of this polymorphism was investigated in 469 individuals from the south of Spain, and was similar to that previously described in other Caucasian populations: 85% A, 14% B and 1% C alleles. We identified two new polymorphisms genetically linked to the C isoform, resulting in the Ser273Phe and Met274Val changes. To assess the functional consequence of the polymorphisms in the receptor, we performed flow cytometric analysis of P-selectin dependent neutrophil-platelet interaction. Neutrophils carrying the shortest C allele and the amino acid variations in residues 273 and 274 exhibited a significantly lower capacity to bind activated platelets than A/B and A/A samples (mean fluorescence intensity of CD42b+ neutrophils 262 versus 303 and 319 respectively, P < 0.05). The distribution of the VNTR was analysed in three case-control studies including 104 cerebrovascular (CVD), 101 coronary heart disease (CHD) and 150 deep venous thrombosis (DVT) patients. The results showed that smaller (B and C) alleles seem to be associated with a lower risk of developing CVD (P = 0.008) but not to be related to CHD or DVT. In conclusion, polymorphisms of the PSGL-1 receptor may influence the neutrophil-platelet binding, and represent a risk factor for CVD.


CB1 receptor selective activation inhibits beta-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons.
Among the wide range of neuro-inflammatory signalling molecules released by beta-amyloid-stimulated astroglial cells, nitric oxide (NO) plays a fundamental role in AD aethiopathogenesis since it directly promotes neuronal tau protein hyperphosphorylation leading to neurofibrillary tangle formation. Synthetic cannabinoids (CBs), via a selective CB1 receptor activation, negatively modulates both iNOS protein expression and NO production induced by pro-inflammatory stimuli. In this study we investigated the role of both the non-selective WIN 55,212-2 and the selective CB1 receptor agonist, ACEA, on: (i) NO production, (ii) iNOS protein expression in (1-42) beta-amyloid peptide (Abeta)-stimulated C6 rat glioma cells and (iii) tau protein hyperphosphorylation in co-cultured differentiated PC12 neurons. Our results demonstrated that synthetic CBs, by a selective CB1 effect, down-regulate iNOS protein expression and NO production in Abeta-stimulated C6 cells. This effect leads, in turn, to a significant and concentration-dependent inhibition of NO-dependent tau protein hyperphosphorylation in co-cultured PC12 neurons. The results of the present study extend our knowledge about the neuroprotective actions of synthetic CBs on Abeta-dependent neurotoxicity in vitro. Furthermore, our study allows us to identify, in the CB1-mediated inhibition of astroglial-derived NO, a new potential target to blunt tau hyperphosphorylation and the consequent related tauopathy in AD.


Evaluation of clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma.
Recent investigations have shown that the widely used clonidine suppression test is sometimes fallible for the diagnosis of pheochromocytoma. A comparative assessment was made of the following suppression and provocation tests, the clonidine suppression test, and the glucagon, metoclopramide, and naloxone provocation tests. The assessment was performed in 6 patients with pheochromocytoma and in 19 patients without pheochromocytoma who were initially suspected of harboring a tumor. BP response did not predict the presence of pheochromocytoma in any test. Plasma norepinephrine (NE) concentrations determined at 120 and 180 min after oral 150 micrograms of clonidine gave false negative results in 2 of the 5 patients with pheochromocytoma tested. Both plasma NE and epinephrine (E) concentrations were measured before and sequentially after each provocative agent. Neither NE nor E responded to 1 mg of glucagon iv in 2 of the 4 patients with pheochromocytoma tested. Determination of the peak level, peak increment, and % peak increment of NE and E following 10 mg of naloxone iv did not distinguish the two groups. The % peak increments of both NE and E in all 4 patients with pheochromocytoma given 5 mg of metoclopramide iv exceeded the mean + 3 SD values of the patients without pheochromocytoma (25 + 28% for NE, and 25 + 42% for E). These results suggested that, when performed with judicious patient selection (ambiguous plasma or urinary catecholamine levels), the measurement of plasma catecholamines in response to metoclopramide can be a useful adjunctive tool in the diagnosis of pheochromocytoma.


Risk preferences, preventive behaviour, and the probability of a loss: Empirical evidence from the COVID-19 pandemic.
A theoretical model of optimal choice under risk, in which an individual chooses the level of prevention to avoid a loss, has the ambiguous prediction that a higher risk-taking preference increases the probability of a loss. To empirically investigate the prediction in the case of COVID-19 with individual-level survey data. Survey data from the Understanding America Study (UAS). The UAS Coronavirus Tracking Survey followed 8628 respondents from March 2020 until July 2021 (29 survey waves) and data was gathered on having contracted COVID-19, vaccination, and preventive behaviour. Separate UAS modules gathered data on individuals' risk preferences; twice before and once during the COVID-19 pandemic. UAS also gathered data on pre-pandemic health and socio-economic status. Combining these data, and dropping missing observations, provided longitudinal data for 4335 respondents (96,370 observations) of whom 530 contracted COVID-19. In support of the theoretical prediction, the empirical findings show that a one-standard deviation higher risk-taking preference is associated with about a one-third higher probability of contracting COVID-19 within two weeks. Furthermore, the findings show that individuals' risk-taking preference is negatively associated with the preventive behaviour of social distancing and not associated with getting vaccinated. There is, however, no support for preventive behaviour being associated with the probability of contracting COVID-19. The exception is for being vaccinated, which is negatively associated with the probability of contracting COVID-19. The findings, therefore, do not support that the positive association of the risk-taking preference with the probability of contracting COVID-19 is mediated through observed preventive behaviour. The findings support the importance of individuals' risk-taking behaviour for contracting COVID-19 and, more generally, the importance of loss prevention as a risk management tool for individuals.


Aging of Chinese bony orbit: automatic calculation based on UNet++ and connected component analysis.
Current research on the aging of bony orbit is usually done manually, which is inefficient and has a large error. In this paper, automatic segmentation of bony orbit based on deep learning and automatic calculation of the parameters of the segmented orbital contour (area and height of bony orbit) are presented. The craniofacial CT scanning data of 595 Chinese were used to carry out three-dimensional reconstruction and output the craniofacial images. The orbital contour images are obtained automatically by UNet++ segmentation network, and then the bony orbital area and height were calculated automatically by connected component analysis. The automatic segmentation method has an Intersection of Union of 95.41% in craniofacial CT images. During the aging, the bony orbital area of males increased with age, while that of females decreased, and the area in male was larger than that in female (P < 0.05). The distance from equal points 10 and 40-90 to the supraorbital rim was significantly larger (P < 0.05). Except for the equal point 90, the distance from equal points to the inferior orbital rim was obviously larger (P < 0.05). In the females, the distance from equal points 50-70 to inferior orbital rim was significantly lower (P < 0.05). The method proposed here can automatically and accurately study image dataset of large-scale bony orbital CT imaging. UNet++ can achieve high-precision segmentation of bony orbital contours. The bony orbital area of Chinese changes with aging, and the bony orbital height changes different between males and females, which may be caused by the different position and degree of orbital bone resorption of males and females in the process of aging.


Risk factors for inflammatory complications following third molar surgery in adults.
To estimate the frequency of inflammatory complications (surgical site infection and alveolar osteitis) following third molar (M3) extraction and identify risk factors for such complications. This study was designed as a prospective cohort study and enrolled a sample composed of subjects having >or=1 M3 extracted as part of the American Association of Oral and Maxillofacial Surgeons' Age-Related Third Molar Study. Predictor variables were categorized as demographic, health status, anatomic, and pathologic factors. The outcome variable was the presence of a postoperative inflammatory complication (ie, surgical site infection or alveolar osteitis). Descriptive and bivariate statistics were computed. Variables with P values less than .15 in bivariate analyses were included in a multiple logistic regression model, used to identify factors associated with inflammatory complications. The study sample consisted of 4,004 subjects with a mean age of 39.8 +/- 13.6 years having 8,748 M3s extracted. In bivariate analyses, impaction level, periodontal disease in or around M3, pre-existing infection around M3, and M3 pathology were associated with postoperative inflammatory complications. In the multiple regression model, level of impaction (soft tissue: odds ratio [OR] = 2.5; 95% confidence interval [CI], 1.7, 3.7), partial bony OR = 4.7 (95% CI, 3.6, 6.1), full bony, 6.0 (95% CI, 4.7, 7.7); P < .0001), and pre-existing infection (OR = 1.3 [95% CI, 1.0, 1.6; P = .05) or pathology (OR = 3.1; 95% CI, 2.2, 4.3; P < .0001) were associated with an increased risk of inflammatory complications following M3 surgery. Level of impaction, pre-existing infection, and pathology were associated with increased risk for postoperative inflammatory complications following M3 surgery.


Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells.
3,3',5-triiodothyronine (T3) is largely generated from thyroxine (T4) by the catalysis of deiodinases in peripheral tissues. Emerging evidences have indicated its broad participation in regulating various metabolic process via protecting tissues from oxidative stress and improving cellular antioxidant capacity. However, the potential correlation between the oxidative stress and conversion of T4 to T3 is still unclear. In the present study, the effects of T3 and T4 on redox homeostasis in HepG2 cells pre-treated with H2O2 was investigated. It revealed that T3 significantly rescued the apoptotic cell death, consistent with an upregulation of cell antioxidant ability and reduction of ROS accumulation while T4 did not. Afterwards, we examined the enzyme activity and mRNA expression of type 1 5'-deiodianse (DIO1), T3 and rT3 level and found that H2O2 reduced both DIO1 activity and expression in a dose-dependent manner, which consequently declined T3 and rT3 generation. Alpha-lipoic acid (LA) treatment notably restored DIO1 activity, T3 and rT3 level, as well as transcriptional abnormalities of inflammation-associated genes. It suggests that oxidative stress may reduce DIO1 activity by an indirect way like activating cellular inflammatory responses. All these results indicate that the oxidative stress downregulates the conversion of T4 to T3 through DIO1 function in HepG2 cells.


An attempt to assess the replacement dose of human growth hormone in the treatment of growth hormone deficient children.
In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3-0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900-2100 hours with a dose of 0.46 +/- 0.07 IU/kg/week (equivalent to 14.7 +/- 2.0 IU/m2/week). After 1-3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.


Subcutaneous metastasis from transitional cell carcinoma of the bladder diagnosed by fine needle aspiration biopsy. A case report.
Metastasis of transitional cell carcinoma (TCC) of the bladder to the skin and subcutaneous tissue is an uncommon finding. A 58-year-old man with a known case of high grade TCC of the bladder, presented with a right paraspinal mass. Clinically an abscess was suspected. Fine needle aspiration (FNA) showed many clusters and isolated malignant cells in an inflammatory background. The smears were diagnosed as positive for malignancy. It is essential to differentiate tumors metastatic to the skin and subcutaneous tissue from inflammatory lesions. FNA helped with the diagnosis in this case and prevented unnecessary biopsy.


Colonic anastomotic strength and matrix metalloproteinase activity in an experimental model of bacterial peritonitis.
Clinical studies report conflicting results on the safety of primary intestinal anastomoses in the presence of peritonitis, and comprehensive experimental data are lacking. The present study investigated whether the strength of experimental colonic anastomoses is affected if surgery is performed in the presence of pre-existing bacterial peritonitis. Colonic anastomoses were constructed in Wistar rats 24 h after caecal ligation and puncture or a sham procedure. Anastomotic strength was assessed by measuring breaking strength and bursting pressure during the first 5 days after operation. Anastomotic hydroxyproline levels were measured and matrix metalloproteinase (MMP) activity was analysed by quantitative gelatin zymography. Anastomotic strength was lowered in the presence of bacterial peritonitis but in a minor and transient way. The breaking strength was lower only immediately after construction of the anastomosis (- 15 per cent, P = 0.011) and the bursting pressure only on the third postoperative day (- 33 per cent, P = 0.038); no anastomotic dehiscence was observed. At 3 days after operation increased levels of MMP activity were observed but anastomotic hydroxyproline content was not affected by bacterial peritonitis. The influence of bacterial peritonitis on the development of anastomotic strength is limited. This experimental finding lends support to recent clinical studies that have demonstrated the feasibility of constructing a primary anastomosis under these conditions.


Quality of Harvested Seed Associated with Soybean Cultivars and Herbicides Under Weed-Free Conditions.
Different herbicides were applied to soybean plants in field plots planted to different soybean cultivars located at four locations in Illinois between 1997 and 2000. Treatments varied from hand weeded to preemergence herbicides to postemergence herbicides. Soybean seeds were harvested and evaluated for different seed quality parameters. The percentage of seeds infected with Phomopsis spp. ranged from 1 to 40%, and the percentage of seeds infected with Cercospora kikuchii was low, ranging from 0 to 4%. Herbicides had little or no effect on seed quality parameters such as percent germination and incidence of seed pathogens or on protein and oil concentrations. Soybean seed quality was affected by Phomopsis spp. in that there were significant (P ≤ 0.05) inverse correlations between Phomopsis spp. incidence and percentage seed germination. It appears that Phomopsis spp. may be a more prevalent seed pathogen than C. kikuchii for soybean fields in central to northern Illinois.


Cell-type-based analysis of microRNA profiles in the mouse brain.
MicroRNAs (miRNA) are implicated in brain development and function but the underlying mechanisms have been difficult to study in part due to the cellular heterogeneity in neural circuits. To systematically analyze miRNA expression in neurons, we have established a miRNA tagging and affinity-purification (miRAP) method that is targeted to cell types through the Cre-loxP binary system in mice. Our studies of the neocortex and cerebellum reveal the expression of a large fraction of known miRNAs with distinct profiles in glutamatergic and GABAergic neurons and subtypes of GABAergic neurons. We further detected putative novel miRNAs, tissue or cell type-specific strand selection of miRNAs, and miRNA editing. Our method thus will facilitate a systematic analysis of miRNA expression and regulation in specific neuron types in the context of neuronal development, physiology, plasticity, pathology, and disease models, and is generally applicable to other cell types and tissues.


A new active learning approach for adsorbate-substrate structural elucidation in silico.
Adsorbate interactions with substrates (e.g. surfaces and nanoparticles) are fundamental for several technologies, such as functional materials, supramolecular chemistry, and solvent interactions. However, modeling these kinds of systems in silico, such as finding the optimum adsorption geometry and energy, is challenging, due to the huge number of possibilities of assembling the adsorbate on the surface. In the current work, we have developed an artificial intelligence (AI) approach based on an active learning (AL) method for adsorption optimization on the surface of materials. AL uses machine learning (ML) regression algorithms and their uncertainties to make a decision (based on a policy) for the next unexplored structures to be computed, increasing, though, the probability of finding the global minimum with a small number of calculations. The methodology allows an accurate and automated structural elucidation of the adsorbate on the surface, based on the minimization of the total electronic energy. The new AL method for adsorption optimization was developed and implemented in the quantum machine learning software/agent for material design and discovery (QMLMaterial) program and was applied for C60@TiO2 anatase (101). It marks another software extension with a new feature in addition to the automatic structural elucidation of defects in materials and of nanoparticles as well. SCC-DFTB calculations were used to build the complex search surfaces with a reasonably low computational cost. An artificial neural network (NN) was employed in the AL framework evaluated together with two uncertainty quantification methods: K-fold cross-validation and non-parametric bootstrap (BS) resampling. Also, two different acquisition functions for decision-making were used: expected improvement (EI) and the lower confidence bound (LCB).


Evidence for nonspecific induction of beta-lactamase in overproducing variants of Enterobacter cloacae and Citrobacter freundii.
Induction of chromosomally mediated beta-lactamases was studied in clinical isolates of Enterobacter cloacae and Citrobacter freundii. Whereas isolates resistant to ampicillin and cefoxitin exhibited an inducible enzyme, those sensitive to both agents did not. Cefoxitin and above all imipenem proved the most efficacious enzyme inducers. Variants among these inducible isolates which produced large amounts of beta-lactamase could be selected in the presence of cefamandole. In each of these selected variants constitutive enzyme production was markedly enhanced by induction, even with compounds lacking induction potency for the corresponding wild strains. Moreover, these variants could also be induced non-specifically, i.e. by non-beta-lactam compounds. Production of large amounts of enzyme was associated with resistance to all available beta-lactam compounds.


Phaeochromocytoma and cardiomyopathy.
This case report describes a patient who presented with severe biventricular cardiac failure and shock, whose cardiac function returned to normal after the removal of a noradrenaline-secreting benign phaeochromocytoma. A catecholamine-induced cardiomyopathy with cardiogenic shock, rather than catecholamine-mediated peripheral vasoconstriction alone, is postulated as a mechanism to account for the marked hypoperfusion.


Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England.
To compare the change in illicit opioid users' risk of fatal drug-related poisoning (DRP) associated with opioid agonist pharmacotherapy (OAP) and psychological support, and investigate the modifying effect of patient characteristics, criminal justice system (CJS) referral and treatment completion. National data linkage cohort study of the English National Drug Treatment Monitoring System and the Office for National Statistics national mortality database. Data were analysed using survival methods. All services in England that provide publicly funded, structured treatment for illicit opioid users. Adults treated for opioid dependence during April 2005 to March 2009: 151,983 individuals; 69% male; median age 32.6 with 442,950 person-years of observation. The outcome was fatal DRP occurring during periods in or out of treatment, with adjustment for age, gender, substances used, injecting status and CJS referral. There were 1499 DRP deaths [3.4 per 1000 person-years, 95% confidence interval (CI) = 3.2-3.6]. DRP risk increased while patients were not enrolled in any treatment [adjusted hazard ratio (aHR) = 1.73, 95% CI = 1.55-1.92]. Risk when enrolled only in a psychological intervention was double that during OAP (aHR = 2.07, 95% CI = 1.75-2.46). The increased risk when out of treatment was greater for men (aHR = 1.88, 95% CI = 1.67-2.12), illicit drug injectors (aHR = 2.27, 95% CI = 1.97-2.62) and those reporting problematic alcohol use (aHR = 2.37, 95% CI = 1.90-2.98). Patients who received only psychological support for opioid dependence in England appear to be at greater risk of fatal opioid poisoning than those who received opioid agonist pharmacotherapy.


Alterations of [3H]actinomycin D binding to axotomized dorsal root ganglion cell nuclei: an autoradiographic method to detect changes in chromatin structure and RNA synthesis.
An autoradiographic method was developed to quantify on a comparative basis the binding of [3H]actinomycin D (Act D) to the cell nuclei of frozen, unfixed sections of spinal sensory ganglia in rats. After a crush lesion of the sciatic nerve, alterations of [3H]Act D binding were found in L5 and L6 dorsal root ganglia which corresponded to changes in RNA synthesis observed in other studies. An increase in Act D binding was seen at 1 to 3 days postoperation, followed by a decrease at 5 to 7 days. By 9 to 11 days a second increase in binding occurred, followed by a decrease at 14 days. Contralateral ganglia exhibited an increase in Act D binding only at 5 days compared with unoperated controls. The timing of the response in axotomized ganglia differed with the distance of the lesion from the cell body. The observed patterns of Act D binding confirm that changes of chromatin structure are closely associated with the alterations of RNA and protein synthesis occurring after axon injury. The method may be useful as an indicator for alterations in RNA synthesis related to changes in chromatin structure in complex tissues.


The Effect of IL-6 Inhibitors on Mortality Among Hospitalized COVID-19 Patients: A Multicenter Study.
The effectiveness of interleukin-6 inhibitors (IL-6i) in ameliorating coronavirus disease 2019 (COVID-19) remains uncertain. We analyzed data for patients aged ≥18 years admitted with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test at 4 safety-net hospital systems with diverse populations and high rates of medical comorbidities in 3 US regions. We used inverse probability of treatment weighting via machine learning for confounding adjustment by demographics, comorbidities, and disease severity markers. We estimated the average treatment effect, the odds of IL-6i effect on in-hospital mortality from COVID-19, using a logistic marginal structural model. Of 516 patients, 104 (20.1%) received IL-6i. Estimate of the average treatment effect adjusted for confounders suggested a 37% reduction in odds of in-hospital mortality in those who received IL-6i compared with those who did not, although the confidence interval included the null value of 1 (odds ratio = 0.63; 95% confidence interval, .29-1.38). A sensitivity analysis suggested that potential unmeasured confounding would require a minimum odds ratio of 2.55 to nullify our estimated IL-6i effect size. Despite low precision, our findings suggested a relatively large effect size of IL-6i in reducing the odds of COVID-19-related in-hospital mortality.


Metrizamide CT cisternography combined with Myodil (Pantopaque) cisternography in the investigation of suspected small acoustic neuromata.
A combined technique for the investigation of suspected small acoustic neuromata, involving the performance of a metrizamide CT cisternogram, a Myodil (Pantopaque) cisternogram, and also an estimation of the CSF protein level, all at the same examination, is described. An entirely negative result excludes an acoustic neuroma. A few illustrative abnormal cases are described.


Isoproterenol-induced changes in glutathione metabolism in the rat parotid gland.
Rat parotid glands were removed at timed intervals after intraperitoneal injection of isoproterenol (IPR). Reduced/oxidized glutathione ratios, glutathione peroxidase, glutathione reductase and amylase activities were determined. Parotid gland amylase content fell to less than 5 per cent of control values within 1 h after IPR, then slowly returned to control levels by 24 h. The ratio of reduced/oxidized glutathione was decreased at 2 h after IPR injection, returned to near control values at 6 h, then increased above control levels at 9, 12 and 24 h. Glutathione peroxidase activity was increased only at 12 h after injection of IPR, whereas glutathione reductase activity initially decreased, then reached peak values at 12 h. These results indicate that alterations in metabolic activity during the secretory cycle are accompanied by changes in the reduced/oxidized glutathione ratio and the activity of glutathione-metabolizing enzymes. Cellular events contributing to these alterations in glutathione metabolism may include exocytosis, endocytosis and membrane recycling, increased amino-acid transport and resynthesis of secretory proteins.


What is the impact of cervical invasion on lymph node metastasis in patients with stage IIIC endometrial cancer?
The aim of this study was to evaluate whether the presence of cervical invasion has altered the site of lymph node (LN) metastasis in stage IIIC endometrial cancer (EC) patients. Fourty-six patients who had systematic pelvic and para-aortic lymphadenectomy surgery for EC and staged as IIIC were included in the study. Patients with cervical invasion were defined as Group A and patients without cervical invasion were defined as Group B. The groups were compared according to surgical-pathologic characteristics. Chi-square and Annova table test were used to examine the effect of cervical invasion on LN metastasis. The mean age of patients was 59 years (range 38-81) and tumor size was 47 mm (range 10-80). Twenty-three patients had cervical involvement (Group A) and 23 had no cervical metastasis (Group B). Groups were not different with regard to cell type, grade, depth of myometrial invasion, tumor size, adnexal involvement, peritoneal metastasis and lymphovascular space invasion. Among 46 patients obturator LN was the most involved site of LN metastasis, however, when there is cervical metastasis external iliac LN was found to be the most involved LN site. Patients without cervical invasion had 21.7% of external iliac LN metastasis while patients with cervical invasion had 60.9% of external iliac LN metastasis. Also, cervical invasion has increased the risk of pelvic LN and obturator LN involvement from 82.6 to 95.7% and 39.1 to 52.2%, respectively. Cervical invasion may have an effect on lymphatic spread and change the site of metastatic LNs. Large prospective studies are needed to clarify the alteration of LN metastasis in cervix invaded EC patients.


CBF before and after extracranial-intracranial bypass surgery in patients with ischemic cerebrovascular disease studied with 133Xe-inhalation tomography.
Cerebral blood flow (CBF) was studied by 133Xenon inhalation tomography in 22 patients with symptoms of ischemic cerebrovascular disease before and after establishment of an extracranial-intracranial bypass shunt. Selection of patients for shunting was based on angiographically demonstrated arterial occlusions and on the finding of focal low flow areas corresponding to the clinical symptoms, that consisted mainly of minor stroke with good remission and with or without subsequent TIAs. It was required that the area of low flow should clearly exceed the CT lesion present in practically all cases. Following surgery, the permanent neurologic deficits remained unchanged, while the TIAs stopped in all but one case. Two patients showed a definite increase of CBF in the low flow area while another two showed a questionable increase. All the other cases, 18 of the 22, showed an unchanged tomographic flow map with no trend towards diminution in extension or severity of the focal hypoperfused area. A persistent low flow in areas with no corresponding CT lesion following alleviation of a possible flow impediment is interpreted to represent an incomplete infarction or diaschisis.


[Intraocular foreign body and endophthalmitis: risk factors and management].
This study aims to identify the risk factors for post-traumatic endophthalmitis (PTE) due to intraocular foreign body (IFB) in patients with penetrating injuries of the globe and to assess treatment outcomes. We conducted a descriptive, retrospective study of 60 patients hospitalized for penetrating wound due to intraocular foreign body at the Hedi Rais Institute of Ophthalmology, Tunis, over a period of 10 years. Our study involved the patients with penetrating ocular trauma due to intraocular foreign body associated with post-traumatic endophthalmitis. We also determined the clinical risk factors for endophthalmitis in these patients. We collected data from the medical records of 60 patients with penetrating injury due to intraocular foreign body. Clinical symptoms of endophthalmitis were reported in ten of these patients (16.66%). All IFBs were located in the posterior segment. Mean LogMAR visual acuity (VA) at baseline was 2.26. Final Mean LogMAR VA was 2.18. We found a statically significant correlation between the occurrence of endophthalmitis and the following factors: rural origin p=0.021, delays in removing IFB p=0.01, posterior location IFB p=0.012, capsule rupture p=0.022, associated retinal detachment p<0.0001. The identification of risk factors for post-traumatic endophthalmitis allow for better treatment adaptation and preventive measures of this complication to improve prognosis and quality of life.


Cancer prevention in primary care. Screening for cervical cancer.
Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk--namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes.


We Don't Choose Whom We Love: Predictors for Romantic Attraction to Villains.
Why are women (not) romantically attracted to dark personalities or villains, which might be a risk factor for intimate partner violence (IPV) victimization? In the current study, it is opted to investigate how adult attachment, maladaptive personality traits, and acceptance of couple violence in women predict romantic attraction to heroic/villainous characters using structural equation modeling (SEM). First, a pilot study was conducted in 122 heterosexual women (aged 16-25) to select male TV characters. This resulted in the selection of six villains and 10 heroes for the main study, in which 194 other heterosexual women (aged 16-25) were asked to rate the pictures of TV characters through an online questionnaire. This was combined with self-report measures of maladaptive personality traits, acceptance of couple violence, and adult attachment. These variables were entered into a SEM model to assess model fit. Overall, women rated heroes higher on physical appearance (pilot study) and romantic attraction (main study) compared to villains. We found different direct effects of avoidant (negative) and anxious (positive) attachment styles on romantic attraction to heroes. Moreover, maladaptive personality traits fully mediated the positive effect of avoidant attachment style on romantic attraction to villains. Despite the limitations of the study design (e.g., low N, low notoriety of the TV characters), this study emphasizes that women are generally more romantically attracted to heroes (vs. villains). Besides, there are different predictors of romantic attraction to heroes and villains, which requires further investigation, especially in the context of IPV.


Partial purification of protein farnesyl cysteine carboxyl methyltransferase from bovine brain.
C-terminal farnesyl cysteine carboxyl methylation has been known to be the last step in the post-translational modification processes of several important signal transduction proteins in eukaryotes including ras related GTP binding proteins and the gamma-subunit of heterotrimeric G proteins. Protein farnesyl cysteine carboxyl methyltransferase (PFCCMT; EC, 22.214.171.124) catalyzing the reaction is well characterized as being stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and suppressed by N-acetyl-S-farnesyl-L-cysteine (AFC). As an initial step to understand the physiological significance of the process, we attempted to purify the enzyme, which was partially purified 130-fold (specific activity, 143 pmol of methyl group transferred/min/mg of protein) with yield of 1.8% after purification by fast protein liquid chromatography (FPLC) on a Superdex 75 column. The enzyme was further purified with non denaturing polyacrylamide gel electrophoresis (ND-PAGE) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight of PFCCMT was determined to be about 30 kDa based on Superdex 75 FPLC as well as photoaffinity labelling with S-adenosyl-L-[methyl-3H] methionine ([methyl-3H]SAM). The partially purified enzyme (Superdex 75 eluate) was found to be characteristically affected by GTP gamma S, being activated about 40-fold in 2 mM, in contrast to ATP which did not show any effect on enzyme activity. Meanwhile, the enzyme was found to be markedly inhibited by AFC, reaching 0 activity in 2 mM. These observations strongly suggested that the partially purified enzyme was PFCCMT.


Effect of an antihypertensive hydrazine derivative on Ca2+ current of single frog cardiac cells.
The effects of MP 518, an acylated 2-chlorobenzylidene hydrazidone derivative with antihypertensive properties were investigated on the Ca current, ICa, recorded under whole-cell patch-clamp in single frog ventricular cells. MP 518 (1-100 microM) had no effect on ICa under control conditions. However, at 10 microM it significantly increased the beta-adrenergic stimulated ICa, an effect similar to that of isobutylmethyl-xanthine (IBMX), a non-specific phosphodiesterase inhibitor. The effects of MP 518 and IBMX were not, however, additive. This positive effect was also observed with both compounds, MP 518 and IMBX, when a submaximal dose of cyclic AMP was intracellularly perfused. In the presence of IBMX or at a high concentration (100 microM), MP 518 had a negative effect on beta-adrenergic stimulated ICa. It was thus considered that the main effect of MP 518 is an antiphosphodiesterase activity, since the increase in ICa induced by low concentrations of MP 518 could be related to inhibition of cAMP degradation; however, at higher concentrations, MP 518 antagonizes beta-adrenergic stimulation, possibly at several levels. Such an antiphosphodiesterase activity can account for the vasorelaxant effects as well as the tachycardic effects of MP 518.


Reoperation for colorectal carcinoma.
In the management of the patient with intra-abdominal recurrence of colorectal carcinoma, surgery remains the primary mode of therapy when cure or significant palliation is anticipated. Appreciation of the importance of close follow-up after primary resection coupled with improved diagnostic modalities has allowed the surgeon not only to detect earlier recurrence but also to select the patients most likely to benefit from resection of recurrent disease. Improved surgical techniques with resultant decreases in the rates of morbidity and mortality have allowed safe hepatic resection of metastatic disease. In selected patients, this procedure produces 5-year survival rates approaching 50%. Although a clear consensus has not been reached, most studies agree that positive prognostic indicators include absence of extrahepatic disease, a small number of intrahepatic lesions, a low CEA level, and a better Dukes stage of the primary. Likewise, in the patient with recurrent disease locally, surgery provides the only means of cure and also plays a significant role in palliation. Aggressive resection with generous surgical margins in patients with contained disease may yield 5-year survival rates approaching 35%. In patients with unresectable disease and even in those with carcinomatosis, palliation can be obtained by surgical therapy. Judgment is necessary in treating these patients both preoperatively and intraoperatively. Surgical intervention for obstruction, perforation, or other anatomic or physiological compromise is often indicated and can improve the quality of life of the patient with intra-abdominal recurrence.


The Smart Choices front-of-package nutrition label. Influence on perceptions and intake of cereal.
Numerous front-of-package (FOP) nutrition labeling systems exist, but it is unclear if such labels influence behavior. A single-summary label called Smart Choices (SC) appeared briefly on products in the United States in 2009. The current study aimed to evaluate (1) the influence the SC symbol has on the serving and consumption of cereal; and (2) the impact of providing calorie and serving size information on a FOP label. Two hundred and sixteen adults were randomized to a high-sugar breakfast cereal that had either (1) no label; (2) the SC symbol; or (3) a modified SC symbol with serving size information. Participants rated perceptions of healthfulness, taste, and purchase intent, estimated calories per serving and poured and ate the cereal for breakfast. Participants in the SC label conditions were better able to estimate calories per serving, but there were no differences across groups on perceptions of healthfulness, taste, purchase intent, and levels of vitamins, and sugar or amount of cereal poured or consumed. These results suggest that calories per serving information on FOP labels can increase knowledge, but the SC symbol had little impact on behavior. Studies examining FOP label influence on purchasing, consumption, and product reformulation are greatly needed to determine label utility.


Humor intervention program for children with chronic diseases.
This study developed and implemented a humor intervention program for school-aged children with chronic diseases. Thirty-three children with atopic dermatitis and type 1 diabetes were divided into experimental and control groups. The experimental group included 17 children while the control group included 16 children. The experimental group participated in 6 weekly sessions of a 60-minute humor intervention. The subject and type of humorous material was collected from a survey of parents and children. Outcome measures assessed pre- and post-intervention included stress, behavior profile scores, and resilience. There was a significant decrease in behavior problems and increase in resiliency in experimental group compared to control group. There was no difference in stress cortisol measures between the groups. This study was the first to examine a humor intervention for children with chronic diseases in South Korea and offers practical implications for humor interventions in pediatric nursing.


Creation of nanostuctures by extreme conditions: high-pressure synthesis of ultrahard nanocrystalline cubic boron nitride.
The synthesis of high-purity bulk nanostructured cubic boron nitride (cBN) at 20 GPa and 1770 K by direct phase transformation of graphite-like BN with an "ideal random layer" structure is reported. The two-times increase of hardness of nano-cBN (H(V) = 85 GPa) with respect to conventional polycrystalline cBN (H(V) ∼ 45 GPa) is evidently a result of nanosize effects.


Psychophysics and the evolution of behavior.
Sensory information allows animals to interpret their environment and make decisions. The ways in which animals perceive and measure stimuli from the social and physical environment guide nearly every decision they make. Thus, sensory perception and associated cognitive processing have a strong impact on behavioral evolution. Research in this area often focuses on the unique properties of the sensory system of an individual species, yet certain relevant features of perception and cognition generally hold across taxa. One such general feature is the proportionally based translation of physical stimulus magnitude into perceived stimulus magnitude. This process has been recognized for over a century, but recent studies have begun to consider how a law of proportional psychophysics, Weber's law, exerts selective force in behavioral evolution.


Pre-mRNA splicing: awash in a sea of proteins.
What's in a spliceosome? More than we ever imagined, according to recent reports employing proteomics techniques to analyze this multi-megadalton machine. As of 1999, around 100 splicing factors were identified (Burge et al., 1999); however, that number has now nearly doubled due primarily to improved purification of spliceosomes coupled with advances in mass spectrometry analyses of complex mixtures. Gratifyingly, most of the previously identified splicing factors were found in the recent mass spec studies. Nonetheless, the number of new proteins emerging with no prior connection to splicing was surprising. Without functional validation, it would be premature to label these proteins as bona fide splicing factors. Yet many were identified multiple times in complexes purified under diverse conditions or from different organisms. Another recurring theme regards the dynamic nature of spliceosomal complexes, which may be even more intricate than previously thought.


Transannular bovine jugular vein monocusp for the reconstruction of severe right ventricular outflow tract obstruction.
Severe right ventricular outflow tract obstruction in tetralogy of Fallot and variants necessitates the use of transannular patch in a significant proportion of children undergoing repair. We have used a Contegra monocusp together with delamination of native leaflet tissue in order to create a functioning pulmonary valve. In total, 18 (2017-2022) consecutive Contegra monocusp implantations were included. Median age and weight were 3.65 [2.00; 9.43] months and 6.12 [4.30; 8.22] kg, respectively. Nine of 18 patients had undergone palliation. Native pulmonary leaflet tissue was recruited to create a single posterior cusp. Contegra monocusp selection was based on the goal to achieve a neoannulus of Z value ≈ 0. Monocusp sizes implanted were 16 [14; 18] mm. Patch plasty of left pulmonary artery (LPA) (9), right pulmonary artery (RPA) (2), and both LPA-RPA (5) were often performed. All patients survived the operation and were discharged home in good health. Median ventilation time and hospital stay were 2 [1; 9] and 12.5 [9; 54] days, respectively. Follow-up duration was 30.68 [3.47; 60.47] months and 100% complete. One patient with well-corrected right ventricular outflow tract died 9.4 months postoperatively, possibly of aspiration. One child with membranous pulmonary atresia needed reoperation (conduit insertion) at 3.5 months of follow-up. Five needed catheter interventions: supravalvar stent (2), LPA stent (3), and RPA stent (1), most of them in the earlier half of the experience. Pulmonary annulus changed from preoperative -3.91 [-5.98; -2.23] to -0.10 [-1.44; 1.92] at discharge; growing proportionally to -0.13 [-3.52; 2.73] at follow-up. Kaplan-Meier freedom from composite dysfunction was 79.25 (95% confidence interval, +13.68%, -31.44%) at 36 months. Recruitment of native leaflets, optimal Contegra monocusp, and commissuroplasty provide an easily replicable technique for achieving a competent, proportionally growing neopulmonary valve. Longer follow-up is needed to determine its impact on delaying a pulmonary valve replacement.


Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University.
The epidemiological characteristics of New Delhi Metallo-β-Lactamase-Producing (NDM) Enterobacteriaceae were analyzed to provide theoretical support for clarifying the distribution characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the hospital environment and early identification of susceptible patients. From January 2017 to December 2021,42 strains of NDM-producing Enterobacteriaceae were gathered from the Fourth Hospital of Hebei Medical University, primarily Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. The micro broth dilution method combined with the Kirby-Bauer method was used to determine the minimal inhibitory concentrations (MICs) of antibiotics. The carbapenem phenotype was detected by the modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM). Carbapenem genotypes were detected by colloidal gold immunochromatography and real-time fluorescence PCR. The results of antimicrobial susceptibility testing showed that all NDM-producing Enterobacteriaceae were multiple antibiotic resistant, but the sensitivity rate to amikacin was high. Invasive surgery prior to culture, the use of excessive amounts of different antibiotics, the use of glucocorticoids, and ICU hospitalization were clinical characteristics of NDM-producing Enterobacteriaceae infection. Molecular typing of NDM-producing Escherichia coli and Klebsiella pneumoniae was carried out by Multilocus Sequence Typing (MLST), and the phylogenetic trees were constructed. Eight sequence types (STs) and two NDM variants were detected in 11 strains of Klebsiella pneumoniae, primarily ST17, and NDM-1. A total of 8 STs and 4 NDM variants were detected in 16 strains of Escherichia coli, mainly ST410, ST167, and NDM-5. For high-risk patients who have CRE infection, CRE screening should be done as soon as feasible to adopt prompt and efficient intervention measures to prevent outbreaks in the hospital.


Zinc, copper & iron contents in cooked foods & estimates of their daily intakes in young hostel residents.
Dietary zinc, copper and iron intakes of 19 men and 11 women (aged 18-25 yr) were determined during three periods of five consecutive days each, using, weighment method and atomic absorption analysis of food samples. Daily zinc, copper and iron intakes of men ranged from 13.1 +/- 1.2 to 15.3 +/- 1.4 mg/d, 1.62 +/- 0.15 to 1.84 +/- 0.17 mg/d and 20.5 +/- 2.8 to 29.1 +/- 4.5 mg/d and of women 8.8 +/- 2.0 to 9.0 +/- 1.6, 1.42 +/- 0.23 to 1.69 +/- 0.62, and 10.0 +/- 2.4 to 14.7 +/- 2.6 mg/d respectively. Cereals provided 67.7 per cent of dietary zinc, 47.7 per cent copper and 62 per cent iron in men and 60 per cent of Zn, 44 per cent of Cu and 59 per cent of Fe in women, suggesting lower contribution of cereals to Cu intakes than Zn and Fe. Men had mineral intakes close to the recommended allowances for Indians, whereas the intakes of women were 30 to 60 per cent lower. When expressed as mg/1000 kcal, lower calorie intakes of women were responsible for their low mineral intakes. Intra-individual variation in mineral intakes was higher (18.39%) than that of energy intakes (14-17%) in both men and women. Phytate: Zn molar ratios were > 15 indicating risk of zinc deficiency in these students.


Organizational readiness to implement task-strengthening strategy for hypertension management among people living with HIV in Nigeria.
Hypertension (HTN) is highly prevalent among people living with HIV (PLHIV), but there is limited access to standardized HTN management strategies in public primary healthcare facilities in Nigeria. The shortage of trained healthcare providers in Nigeria is an important contributor to the increased unmet need for HTN management among PLHIV. Evidence-based TAsk-Strengthening Strategies for HTN control (TASSH) have shown promise to address this gap in other resource-constrained settings. However, little is known regarding primary health care facilities' capacity to implement this strategy. The objective of this study was to determine primary healthcare facilities' readiness to implement TASSH among PLHIV in Nigeria. This study was conducted with purposively selected healthcare providers at fifty-nine primary healthcare facilities in Akwa-Ibom State, Nigeria. Healthcare facility readiness data were measured using the Organizational Readiness to Change Assessment (ORCA) tool. ORCA is based on the Promoting Action on Research Implementation in Health Services (PARIHS) framework that identifies evidence, context, and facilitation as the key factors for effective knowledge translation. Quantitative data were analyzed using descriptive statistics (including mean ORCA subscales). We focused on the ORCA context domain, and responses were scored on a 5-point Likert scale, with 1 corresponding to disagree strongly. Fifty-nine healthcare providers (mean age 45; standard deviation [SD]: 7.4, 88% female, 68% with technical training, 56% nurses, 56% with 1-5 years providing HIV care) participated in the study. Most healthcare providers provide care to 11-30 patients living with HIV per month in their health facility, with about 42% of providers reporting that they see between 1 and 10 patients with HTN each month. Overall, staff culture (mean 4.9 [0.4]), leadership support (mean 4.9 [0.4]), and measurement/evidence-assessment (mean 4.6 [0.5]) were the topped-scored ORCA subscales, while scores on facility resources (mean 3.6 [0.8]) were the lowest. Findings show organizational support for innovation and the health providers at the participating health facilities. However, a concerted effort is needed to promote training capabilities and resources to deliver services within these primary healthcare facilities. These results are invaluable in developing future strategies to improve the integration, adoption, and sustainability of TASSH in primary healthcare facilities in Nigeria. NCT05031819.


Sex differences in the parental behavior of rodents.
The reproductive strategy of many mammalian species that give birth to altricial young involves intense and prolonged care of their offspring. In most cases, the mother provides all nurturance, but in some cases fathers, older siblings, or unrelated conspecifics participate in parental care. The display of these behaviors by animals other than mothers is affected by numerous factors, including their sex. We herein review the literature on similarities and/or differences between male and female laboratory rodents (rats, mice, voles, gerbils, and hamsters) in their parental responsiveness and discuss how the parental behavior of males and females is influenced by hormones, developmental processes, and prior social experiences. Understanding the mechanisms that generate sex differences in the parental responsiveness of rodents may indicate how similar sex differences in parental care are generated in other mammals.


Facilitation of mouse neuromuscular transmission by propylene glycol.
Propylene glycol (PG) has an excitatory effect on the skeletal muscle of the frog. To determine whether PG has a facilitating effect on the neuromuscular transmission of the mammalian as well as on that of the amphibian and to elucidate the mode of action, we have investigated the effects of PG on the neuromuscular junction of the mouse. PG (1.0% v/v) significantly increased the amplitude of endplate potential. PG raised the frequency of miniature endplate potential and increased its amplitude. PG increased the mean quantal content of the endplate potential. These results indicate that PG facilitates the mouse neuromuscular transmission by accelerating the transmitter release from the nerve terminals and by raising the acetylcholine sensitivity of the endplates.


Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.
Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions. We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4+ T-cell count of 50 cells per μL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107. Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection. Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained. National Institutes of Health and National Cancer Institute.


The effect of canopy filtered light on the growth of white clover Trifolium repens.
Plants of white clover (Trifolium repens) were grown under canopies of clover leaves floating on shallow glass tanks of water and their growth was compared with that of plants under canopies of black polythene 'leaves'. The experimental design allowed the growth of the clover plants in canopy filtered light to be compared with that in unfiltered light at different intensities of Photosynthetically Active Radiation (P.A.R.). The effect of canopy filtered light was to exaggerate the effects of reduced P.A.R. especially in promoting petiole extension and inhibiting stolon branching. Two clones of white clover differed in their responses to P.A.R. and to light quality and there were significant interactions between the effects of the intensity of P.A.R. and type of shade. It is argued that it may be important for both ecologists and plant breeders to recognise the role of radiation quality in regulating the dynamics of pasture.


Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease.
CD4 helper T cells are critical for proper immune cell homeostasis and host defense but are also major contributors to immune and inflammatory disease. Arising from a simple biphasic model of differentiation (ie, TH1 and TH2 cells). A bewildering number of fates seem possible for helper T cells. To what extent different helper cell subsets maintain their characteristic gene expression profiles or exhibit functional plasticity is a hotly debated topic. In this review we will discuss how the expression of "signature cytokines" and "master regulator" transcription factors do not neatly conform to a simple helper T-cell paradigm. Although this might seem confusing, the good news is that the newly recognized complexity fits better with our understanding of immunopathogenesis. Finally, we will discuss factors, including epigenetic regulation and metabolic alterations, that contribute to helper cell specificity and plasticity.


The Psychomotor Vigilance Test Compared to a Divided Attention Steering Simulation in Patients with Moderate or Severe Obstructive Sleep Apnea.
Sleepiness at the wheel affects 10% to 15% of drivers and is one major cause of death on highways with one-third of fatal accidents. Obstructive sleep apnea (OSA) is one of the most common sleep disorders leading to sleepiness at the wheel. The aim of this study was to compare the psychomotor vigilance test reaction time (PVT RT) in OSA patients and controls (morning and afternoon) with the results of a divided attention steering simulator (DASS). A second purpose was to compare these results with the mean sleep latencies in the multiple sleep latency test (MSLT), the Epworth Sleepiness Scale (ESS) values and a neurocognitive test (test of attentional performance, TAP). Thirty eight OSA patients and 16 age and sex matched healthy controls were investigated by ESS, PVT, TAP, MSLT, and DASS (response time, failed responses, lane deviation, and off-road-events). With increasing age, the performance in the DASS decreased. There was no correlation between the DASS and the results of the MSLT and ESS. The controls showed a significantly faster DASS response time in the morning compared to OSA patients (median 2.1 versus 3.0; p=0.044) and fewer off-road events (9 versus 37; p=0.042). We found a moderate correlation between the PVT RT and all parameters of the DASS, as well as the TAP "alertness" subtest. The increase of PVT RT as well as the decreased tonic alertness in the TAP in untreated OSA patients correlated with an impairment of simulated driving performance. The PVT and the TAP are both suitable diagnostic tools for measuring impaired driving ability in OSA patients. The MSLT did not correlate with the simulated driving performance. We recommend investigation of a longer version of the PVT in order to increase its sensitivity.


A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene.
Vitamin-D-dependent rickets 1A (VDDR-1A) is caused by mutations of the renal CYP27B1 gene and is a rare form of rickets. Herein, we report a 20-month-old toddler who presented with inability to walk and failure to thrive. The clinical, biochemical and radiological findings were consistent with a diagnosis of rickets, specifically of the genetic type due to increased 25-OH vitamin D stores. Our patient was a compound heterozygote with 2 novel mutations: c.242G>A(p.Gly81Glu) and c.1144C>G (p.Pro382Ala) in the CYP27B1 gene. Analysis of both mutations with in silico models predicted a deleterious effect on 25-OH vitamin D 1α-hydroxylase function. Interestingly, the levels of 1,25-(OH)2 vitamin D were within normal limits. Our patient was initiated on 1α-hydroxyvitamin D (alfacalcidol) and supplemental calcium. Monitoring of bone metabolism showed a normalization of all bone metabolism serum indices after 3 months of therapy and, thereafter, only alfacalcidol was given at a maintenance dose. The clinical follow-up showed a dramatic improvement in musculoskeletal activity, and the patient regained acceleration in height and weight appropriate for his age. This rare case report of VDDR-1A with normal levels of 1,25-(OH)2 vitamin D enhances our awareness for this type of rickets in clinical practice.


NKAP acts with HDAC3 to prevent R-loop associated genome instability.
Persistent R-loop accumulation can cause DNA damage and lead to genome instability, which contributes to various human diseases. Identification of molecules and signaling pathways in controlling R-loop homeostasis provide important clues about their physiological and pathological roles in cells. Here, we show that NKAP (NF-κB activating protein) is essential for preventing R-loop accumulation and maintaining genome integrity through forming a protein complex with HDAC3. NKAP depletion causes DNA damage and genome instability. Aberrant accumulation of R-loops is present in NKAP-deficient cells and leads to DNA damage and DNA replication fork progression defects. Moreover, NKAP depletion induced R-loops and DNA damage are dependent on transcription. Consistently, the NKAP interacting protein HDAC3 exhibits a similar role in suppressing R-loop associated DNA damage and replication stress. Further analysis uncovers that HDAC3 functions to stabilize NKAP protein, independent of its deacetylase activity. In addition, NKAP prevents R-loop formation by maintaining RNA polymerase II pausing. Importantly, R-loops induced by NKAP or HDAC3 depletion are processed into DNA double-strand breaks by XPF and XPG endonucleases. These findings indicate that both NKAP and HDAC3 are novel key regulators of R-loop homeostasis, and their dysregulation might drive tumorigenesis by causing R-loop associated genome instability.


Child abuse and the legal system: the orthopaedic surgeon's role in diagnosis.
Orthopaedic surgeons have unique training and experience in diagnosis of fractures, both accidental and nonaccidental. That experience is valuable in identifying physical child abuse and in avoiding false accusations or convictions. Both aspects are important to the welfare of children and their families. The events that follow a report of child abuse are outside the training and experience of most orthopaedic surgeons. What process follows a report of suspected child abuse? What unexpected outcomes or results occur in this process? Are medical conclusions used in this process consistent with the state of our knowledge? The child abuse legal process is described as experienced by one orthopaedic surgeon. Examples of unexpected problems that occurred in cases that went to trial are described. Inappropriate outcomes can result from incomplete or incorrectly applied information. The input of the orthopaedic surgeon is often needed to provide the best information available to ensure that the best interests of the child and the family are protected. Working within a hospital team is the preferred method, but direct courtroom testimony is sometimes necessary.


Ribonucleolytic activity of bovine spermatozoal plasma and acrosomal membranes.
We show here the presence of an integral, strong RNAase-A-like ribonucleolytic activity in the plasma and outer acrosomal membranes of bovine spermatozoa. A part of this activity is extractable by salt or detergent.


Intravitreal ranibizumab and bevacizumab in combination with full-fluence verteporfin therapy and dexamethasone for exudative age-related macular degeneration.
To evaluate the efficacy and safety of triple therapy with intravitreal anti-vascular-endothelial-growth-factor (VEGF) antibody, dexamethasone and verteporfin photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). Retrospective, comparative, interventional study. Records of treatment-naïve patients who received intravitreal bevacizumab or ranibizumab in monotherapy or in combination with dexamethasone and full-fluence verteporfin PDT in triple therapy were reviewed. logMAR visual acuity, foveal thickness (FT) on optical coherence tomography, intraocular pressure and endophthalmitis occurrence were recorded. Sixty-one eyes were included in the triple-therapy group, 40 eyes were included in the monotherapy group. The mean follow-up was 14.1 ± 3.4 months in the triple-therapy group and 16.3 ± 4.1 months in the monotherapy group. The triple-therapy group enjoyed a lower total number of treatments (1.92 ± 0.44 vs. 3.12 ± 0.37, p < 0.001) and a longer time before first retreatment (5.4 ± 3.3 vs. 3.6 ± 2.5 months, p = 0.001). A significant improvement of visual acuity and FT was present in both groups during the 12 months following first treatment. No adverse effects were observed. The combination of intravitreal bevacizumab or ranibizumabwith dexamethasone and full-fluence PDT for exudative AMD provided visual and anatomic improvement and a good safety profile. Triple therapy may reduce the number of retreatments when compared to anti-VEGF alone.


Peel bond strength of resilient liner modified by the addition of antimicrobial agents to denture base acrylic resin.
In order to prolong the clinical longevity of resilient denture relining materials and reduce plaque accumulation, incorporation of antimicrobial agents into these materials has been proposed. However, this addition may affect their properties. This study evaluated the effect of the addition of antimicrobial agents into one soft liner (Soft Confort, Dencril) on its peel bond strength to one denture base (QC 20, Dentsply). Acrylic specimens (n=9) were made (75x10x3 mm) and stored in distilled water at 37 ºC for 48 h. The drug powder concentrations (nystatin 500,000 U--G2; nystatin 1,000,000 U--G3; miconazole 125 mg--G4; miconazole 250 mg--G5; ketoconazole 100 mg - G6; ketoconazole 200 mg--G7; chlorhexidine diacetate 5%--G8; and 10% chlorhexidine diacetate--G9) were blended with the soft liner powder before the addition of the soft liner liquid. A group (G1) without any drug incorporation was used as control. Specimens (n=9) (75x10x6 mm) were plasticized according to the manufacturers' instructions and stored in distilled water at 37 ºC for 24 h. Relined specimens were then submitted to a 180-degree peel test at a crosshead speed of 10 mm/min. Data (MPa) were analyzed by analysis of variance (α=0.05) and the failure modes were visually classified. No significant difference was found among experimental groups (p=0.148). Cohesive failure located within the resilient material was predominantly observed in all tested groups. Peel bond strength between the denture base and the modified soft liner was not affected by the addition of antimicrobial agents.


Ascites in children with extrahepatic portal venous obstruction: Etiology, risk factors and outcome.
Ascites in extrahepatic portal venous obstruction (EHPVO) is uncommon. We studied the etiology and natural history of ascites and risk factors of post-bleeding ascites in children with EHPVO. All admitted EHPVO patients with clinically detectable ascites and/or gastrointestinal (GI) bleeding in previous 6 weeks were analysed. Subjects with ascites were classified as post-bleeding ascites and de-novo ascites (no GI bleeding) Post-bleeding ascites group was compared with controls (GI bleeding without ascites) for risk factors of developing ascites. Of the total 307 analysed EHPVO patients, 26% (n=79) had ascites. Majority (n=66, 83%) were post-bleeding ascites and 17% (n=13) had de-novo ascites due to secondary causes. Risk factors of ascites in post-bleeding ascites (n=56) versus controls (n=188) were younger age of disease onset, lower height z-scores and greater reduction in serum protein, albumin and hemoglobin from baseline non-bled state. 32%, 39%, and 29% of patients with post-bleeding ascites had ascites resolution with salt restriction, additional diuretics and large volume paracentesis respectively. Majority of ascites in EHPVO children is after GI bleeding where early age of disease onset, large volume of blood loss and poor nutritional status are risk factors. Overall outcome of EHPVO with ascites is favourable.