Concurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.
Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.


One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.
PURPOSE Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). CONCLUSION We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.


Chromosome number variation and evolution in Neotropical Leguminoseae (Mimosoideae) from northeastern Brazil.
Most members of the subfamily Mimosoideae have pantropical distributions, variable habits, and a basic chromosome number x = 13. We examined karyotypic evolution of 27 species of this subfamily occurring principally in northeastern Brazil by examining chromosomes stained with Giemsa. All of the species had semi-reticulated interphase nuclei and early condensing segments in the proximal region of both chromosome arms. The basic number x = 13 was the most frequent, with 2n = 2x = 26 in 19 of the species, followed by 2n = 4x = 52 and 2n = 6x = 78. However, the three species of the genus Calliandra had the basic number x = 8, with 2n = 2x = 16, while Mimosa cordistipula had 2n = 4x = 32. The karyotypes were relatively symmetrical, although bimodality was accentuated in some species, some with one or two acrocentric pairs. As a whole, our data support earlier hypotheses that the Mimosoideae subfamily has a basic number of x = 13 and underwent karyotypic evolution by polyploidy. However, x = 13 seems to be a secondary basic number that originated from an ancestral stock with x₁ = 7, in which polyploidy followed by descending disploidy gave rise to the current lineages with x = 13. Another lineage, including current representatives of Calliandra with x = 8, may have arisen by ascending disploidy directly from an ancestral monoploid stock with x₁ = 7.


Phosphorus requirement of finishing feedlot calves.
Dietary P supplied to feedlot cattle is important because an inadequate supply will compromise performance, whereas excess P may harm the environment. However, P requirements of feedlot cattle are not well documented. Therefore, 45 steer calves (265.2+/-16.6 kg) were individually fed to determine the P required for gain and bone integrity over a 204-d finishing period. The basal diet consisted of 33.5% high-moisture corn, 30% brewers grits, 20% corn bran, 7.5% cottonseed hulls, 3% tallow, and 6% supplement. Treatments consisted of 0.16 (no supplemental inorganic P), 0.22, 0.28, 0.34, and 0.40% P (DM basis). Supplemental P was provided by monosodium phosphate top-dressed to the daily feed allotment. Blood was sampled every 56 d to assess P status. At slaughter, phalanx and metacarpal bones were collected from the front leg to determine bone ash and assess P resorption from bone. Dry matter intake and ADG did not change linearly (P > 0.86) or quadratically (P > 0.28) due to P treatment. Feed efficiency was not influenced (P > 0.30) by P treatment and averaged 0.169. Plasma inorganic P averaged across d 56 to 204 responded quadratically, with calves fed 0.16% P having the lowest concentration of plasma inorganic P. However, plasma inorganic P concentration (5.7 mg/dL) for steers fed 0.16% P is generally considered adequate. Total bone ash weight was not influenced by dietary P for phalanx (P = 0.19) or metacarpal bones (P = 0.37). Total P intake ranged from 14.2 to 35.5 g/d. The NRC (1996) recommendation for these calves was 18.7 g/d, assuming 68% absorption. Based on performance results, P requirements for finishing calves is < 0.16% of diet DM or 14.2 g/d. Based on these observations, we suggest that typical grain-based feedlot cattle diets do not require supplementation of inorganic mineral P to meet P requirements.


Reduction of fibrogenesis by selective delivery of a Rho kinase inhibitor to hepatic stellate cells in mice.
One of the pathways activated during liver fibrosis is the Rho kinase pathway, which regulates activation, migration, and contraction of hepatic stellate cells (HSC). Inhibition of this kinase by the Rho kinase inhibitor Y27632 [(+)-(R)-trans- 4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] has been shown to reduce fibrosis in animal models. However, kinase expression is ubiquitous, so any inhibitor may affect many cell types. We hypothesize that cell-specific delivery of a kinase inhibitor will be beneficial. Therefore, we conjugated Y27632 to the carrier mannose-6-phosphate (M6P) human serum albumin (HSA), which is taken up specifically in activated HSC through the M6P/insulin-like growth factor II receptor. This conjugate decreased protein expression of phosphorylated myosin light chain 2 (pMLC2) and vinculin, downstream of Rho kinase, in activated primary HSC and decreased the migration and contraction of HSC. In an ex vivo model, free Y27632 decreased contractility of rat aortas, whereas the Y27-conjugate did not, showing that the Y27-conjugate does not affect nontarget tissue. In chronic CCl(4)-induced liver fibrosis, both free drug and conjugate reduced HSC activation; however, only the Y27-conjugate significantly reduced collagen deposition. Treatment with the Y27-conjugate, but not with free drug, reduced pMLC2 expression in livers 24 h after injection, demonstrating prolonged inhibition of the Rho kinase pathway. The Rho kinase inhibitor Y27632 can be specifically targeted to HSC using M6PHSA, decreasing its effects in nontarget tissues. The targeted drug effectively reduced fibrotic parameters in vivo via the inhibition of the Rho kinase pathway.


Identification of UT-A1- and AQP2-interacting proteins in rat inner medullary collecting duct.
The urea channel UT-A1 and the water channel aquaporin-2 (AQP2) mediate vasopressin-regulated transport in the renal inner medullary collecting duct (IMCD). To identify the proteins that interact with UT-A1 and AQP2 in native rat IMCD cells, we carried out chemical cross-linking followed by detergent solubilization, immunoprecipitation, and LC-MS/MS analysis of the immunoprecipitated material. The analyses revealed 133 UT-A1-interacting proteins and 139 AQP2-interacting proteins, each identified in multiple replicates. Fifty-three proteins that were present in both the UT-A1 and the AQP2 interactomes can be considered as mediators of housekeeping interactions, likely common to all plasma membrane proteins. Among proteins unique to the UT-A1 list were those involved in posttranslational modifications: phosphorylation (protein kinases Cdc42bpb, Phkb, Camk2d, and Mtor), ubiquitylation/deubiquitylation (Uba1, Usp9x), and neddylation (Nae1 and Uba3). Among the proteins unique to the AQP2 list were several Rab proteins (Rab1a, Rab2a, Rab5b, Rab5c, Rab7a, Rab11a, Rab11b, Rab14, Rab17) involved in membrane trafficking. UT-A1 was found to interact with UT-A3, although quantitative proteomics revealed that most UT-A1 molecules in the cell are not bound to UT-A3. In vitro incubation of UT-A1 peptides with the protein kinases identified in the UT-A1 interactome revealed that all except Mtor were capable of phosphorylating known sites in UT-A1. Overall, the UT-A1 and AQP2 interactomes provide a snapshot of a dynamic process in which UT-A1 and AQP2 are produced in the rough endoplasmic reticulum, processed through the Golgi apparatus, delivered to endosomes that move into and out of the plasma membrane, and are regulated in the plasma membrane.


Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro.
SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.


Factors targeting MED12 to drive tumorigenesis?
Mediator Subcomplex 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations of its gene predominantly occur in two types of highly frequent benign tumors, uterine leiomyomas and fibroadenomas of the breast, where they apparently act as driver mutations. Nevertheless, their presence is not restricted to benign tumors having been found at considerable frequencies in uterine leiomyosarcomas, malignant phyllodes tumors, and chronic lymphocytic leukemia also. Most of the mutations are located within exon 2 of the gene but in rare cases the intron 1/exon 2 boundary or exon 1 are affected. As to their type, predominantly single nucleotide exchanges with a hotspot in one codon are found, but small deletions clustering around that hotspot also are not uncommon. According to their presumed classification as gain-of-function mutations, these latter deletions are leaving the open reading frame intact. As to the types of mutations, so far no apparent differences between the tumor entities affected have emerged. Interestingly, this pattern with small deletions clustered around the hotspot of single nucleotide exchanges resembles that seen as a result of targeted gene editing. In contrast to other driver mutations the percentage of MED12-mutation positive tumors of independent clonal origin increases with the number of tumors per patient suggesting unknown etiological factors supporting site specific mutagenesis. These factors may act by inducing simultaneous site-specific double strand breaks the erroneous repair of which may lead to corresponding mutations. As inducers of DNA damage and its repair such as foreign nucleic acids of the microbiome displaying sequence homology to the putative target site might play a role. Interestingly, a 16 base pair homology of the hotspot to a putative terminator base-paired hairpin sequence of a Staphylococcus aureus tRNA gene cluster has been noted which might form R-loop like structures with its target sequence thus inducing said changes.


Does acute TBI-related sleep disturbance predict subsequent neuropsychiatric disturbances?
To determine whether sleep disturbance in the acute post-traumatic brain injury (TBI) period predicts symptoms of depression, anxiety or apathy measured 6 and 12 months after TBI. Longitudinal, observational study. First time closed-head injury patients (n = 101) were recruited and evaluated within 3 months of injury and followed longitudinally, with psychiatric evaluations at 6 and 12 months post-injury. Pre- and post-injury sleep disturbances were measured via the Medical Outcome Scale (MOS) for Sleep. Subjects were also assessed for anxiety, depression, apathy, medical comorbidity and severity of TBI. Sleep disturbance in the acute TBI period was associated with increased symptoms of depression, anxiety and apathy 12 months post-injury. Sleep disturbances experienced soon after trauma (i.e. <3 months after injury) predicted neuropsychiatric symptoms 1 year after injury, raising two important clinical questions: (1) Is sleep disturbance soon after trauma a prognostic marker of subsequent neuropsychiatric symptoms? and (2) Can early treatment of sleep disturbance during the post-TBI period reduce subsequent development of neuropsychiatric symptoms? Future studies with larger sample sizes and appropriate control groups could help to answer these questions, using evidence-based methods for evaluating and treating sleep disturbances.


Effects of Duration and Midpoint of Sleep on Corticolimbic Circuitry in Youth.
Adequate sleep is essential for cognitive and emotion-related functioning, and 9 to 12 hr of sleep is recommended for children ages 6 to 12 years and 8 to 10 hr for children ages 13 to 18 years. However, national survey data indicate that older youth sleep for fewer hours and fall asleep later than younger youth. This shift in sleep duration and timing corresponds with a sharp increase in onset of emotion-related problems (e.g., anxiety, depression) during adolescence. Given that both sleep duration and timing have been linked to emotion-related outcomes, the present study tests the effects of sleep duration and timing, and their interaction, on resting-state functional connectivity (RS-FC) of corticolimbic emotion-related neural circuitry in children and adolescents. A total of 63 children and adolescents (6-17 years, 34 females) completed a weekend overnight sleep journal and a 10-min resting-state functional magnetic resonance imaging scan the next day (Sunday). Whole-brain RS-FC of the amygdala was computed, and the effects of sleep duration, timing (i.e., midpoint of sleep), and their interaction were explored using regression analyses. Overall, we found that older youth tended to sleep later and for fewer hours than younger youth. Controlling for age, shorter sleep duration was associated with lower RS-FC between the amygdala and regions implicated in emotion regulation, including ventral anterior cingulate cortex, precentral gyrus, and superior temporal gyrus. Interestingly, midpoint of sleep was associated with altered connectivity in a distinct set of brain regions involved in interoception and sensory processing, including insula, supramarginal gyrus, and postcentral gyrus. Our data also indicate widespread interactive effects of sleep duration and midpoint on brain regions implicated in emotion regulation, sensory processing, and motor control. These results suggest that both sleep duration and midpoint of sleep are associated with next-day RS-FC within corticolimbic emotion-related neural circuitry in children and adolescents. The observed interactive effects of sleep duration and timing on RS-FC may reflect how homeostatic and circadian process interact in the brain and explain the complex patterns observed with respect to emotional health when considering sleep duration and timing. Sleep-related changes in corticolimbic circuitry may contribute to the onset of emotion-related problems during adolescence.


Anxiety and Ironic Errors of Performance: Task Instruction Matters.
Five experiments that examined Wegner's theory of ironic processes of mental control in reactive motor performance under pressure are presented for the first time. In Experiments 1, 2, and 4, the authors conducted specific examinations of the incidence of an ironic error using a reactive motor task. In Experiments 3 and 5, they provided the first tests of whether task instruction moderates the incidence of ironic errors. The task required participants to react to a series of three primary-colored balls as they rolled down a chute under low- and high-anxiety conditions. Measures of anxiety, heart rate, heart-rate variability, and muscle activity confirmed the effectiveness of the anxiety manipulation. Experiments 1, 2, and 4 revealed that anxiety increased the number of ironic errors. In Experiments 3 and 5, the authors provided the first evidence that instructional interventions can reduce the incidence of anxiety-induced ironic performance errors in reactive motor tasks.


Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in-vitro culture in cryopreservation studies.
Development of in vitro culture protocol for early stage ovarian follicles of zebrafish is important since cryopreserved early stage ovarian follicles would need to be matured in vitro following cryopreservation before they can be fertilised. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in vitro culture of early stage zebrafish ovarian follicles in ovarian tissue fragments is reported here for the first time although some work has been reported for in vitro culture of isolated early stage zebrafish ovarian follicles. The main aim of the present study was to develop molecular markers in an optimised in vitro culture protocol for stage I and stage II zebrafish ovarian follicles in ovarian tissue fragments. The effect of concentration of the hormones human chorionic gonadotropin and follicle stimulating hormones, and additives such as Foetal Bovine Serum and Bovine Serum Albumin were studied. The results showed that early stage zebrafish ovarian fragments containing stage I and stage II follicles which are cultured in vitro for 24 h in 20% FBS and 100mIU/ml FSH in 90% L-15 medium at 28 °C can grow to the size of stage II and stage III ovarian follicles respectively. More importantly the follicle growth from stage I to stage II and from stage II to stage III were confirmed using molecular markers such as cyp19a1a (also known as P450aromA) and vtg1 genes respectively. However, no follicle growth was observed following cryopreservation and in vitro culture.


Positive predictive value of first-time rheumatoid arthritis diagnoses and their serological subtypes in the Danish National Patient Registry.
To assess whether the positive predictive value (PPV) of first-time rheumatoid arthritis (RA) diagnosis registration in the Danish National Patient Registry increases when data are linked to the RA treatment codes and to assess the PPV of first-time RA diagnoses according to RA serological subtypes. Participants from the Danish Diet, Cancer, and Health cohort with at least one RA diagnosis, registered at one of the Central Denmark Region hospitals in the Danish National Patient Registry during the period 1977-2016, were identified. Register-based RA diagnoses were verified by scrutinizing medical records against RA classification criteria or clinical case RA. PPVs for overall RA, seropositive RA, and other RA were calculated for two models: first-time RA diagnosis registration ever in the Danish National Patient Registry and first-time RA diagnosis registration ever where subsequently a prescription had been redeemed for a synthetic disease-modifying antirheumatic drug. Overall, 205 of 311 first-time register-based RA diagnoses were verified (PPV: 61.9%; 95% CI: 56.9-67.0). Regarding RA serological subtypes, 93 of 150 register-based seropositive RA (PPV: 62.0; 95% CI: 53.9-69.5) and 36 of 144 other RA (PPV: 25.0; 95% CI: 18.5-32.8) were confirmed. When register-based RA diagnosis codes were linked to RA treatment codes, the PPVs increased substantially: the PPV for overall RA was 87.7% (95% CI: 82.5-91.5), the PPV for seropositive RA was 80.2% (95% CI: 71.6-86.7), and the PPV for other RA was 41.1% (95% CI: 30.2-52.9). The first-time RA diagnoses in the Danish National Patient Registry should be used with caution in epidemiology research. However, linking registry-based RA diagnoses to the subsequent RA treatment codes increases the probability of identifying true RA diagnoses, especially overall RA and seropositive RA.


Expression analysis of histone acetyltransferases in rice under drought stress.
Histone acetylation is one of the vital reversible modifications of chromatin structure that regulates gene expression in eukaryotes. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) maintain the homeostasis of histone acetylation. Studies in Arabidopsis have revealed that HATs are involved in plant responses to various stresses including light, temperature, salt and ABA. Drought stress, a very common environmental stress, could cause a range of physiological and biochemical responses in plants involving HATs. Eight HATs in four different families (CBP, GNAT, MYST, and TAF(II)250 family) are known in rice. In this research, four OsHATs, one from each family, were chosen based on in silico domain and promoter analysis for their response under drought conditions. Drought stress was introduced to two-leaf-stage rice seedlings. The effectiveness of drought treatment was confirmed by the measurement of relative water content (RWC). Real-time quantitative polymerase chain reaction analysis demonstrated that drought stress caused a significant increase in the expression of four HATs (OsHAC703, OsHAG703, OsHAF701 and OsHAM701) in rice plants. Additionally, the Western-blot analysis showed that the acetylation level on certain lysine sites of H3 (lysine 9, lysine 18 and lysine 27) and H4 (lysine 5) increased with OsHATs expression. The significant increase in the transcript levels of OsHATs and the acetylation level of lysine residues on Histone H3 and H4 suggest that OsHATs are involved in drought stress responses in rice.


The surgical implications of herniation of the urinary bladder.
The urinary bladder is often involved in an inguinal hernia, but herniation of the entire bladder into the scrotum is rare. As many as 4% of inguinal hernias may involve the bladder, usually in the form of a sliding hernia. Most urinary bladder herniations are diagnosed at the time of inguinal herniorrhaphy, and are therefore most commonly repaired through an inguinal incision. If the diagnosis requires amendment, alternative surgical approaches are available. We studied two patients with massive inguinoscrotal herniation of the urinary bladder, commonly referred to as "scrotal cystocele." We reviewed the literature, incidence, causes, diagnosis, and surgical consideration of herniation of the urinary bladder, and gave particular attention to the interrelationship of bladder herniations with inguinal hernias.


Organization of gene and non-gene sequences in micronuclear DNA of Oxytricha nova.
In order to study the derivation of the macronuclear genome from the micronuclear genome in Oxytricha nova micronuclear DNA was partially digested with EcoRI, size fractionated, and then cloned in the lambda phage Charon 8. Clones were selected a) at random b) by hybridization with macronuclear DNA or c) by hybridization with clones of macronuclear DNA. One group of these clones contains only unique sequence DNA, and all of these had sequences that were homologous to macronuclear sequences. The number of macronuclear genes with sequences homologous to these micronuclear clones indicates that macronuclear sequences are clustered in the micronuclear genome. Many micronuclear clones contain repetitive DNA sequences and hybridize to numerous EcoRI fragments of total micronuclear DNA, yielding similar but non-identical patterns. Some micronuclear clones containing these repetitive sequences also contained unique sequence DNA that hybridized to a macronuclear sequence. These clones define a major interspersed repetitive sequence family in the micronuclear genome that is eliminated during formation of the macronuclear genome.


Water-protein interactions: the secret of protein dynamics.
Water-protein interactions help to maintain flexible conformation conditions which are required for multifunctional protein recognition processes. The intimate relationship between the protein surface and hydration water can be analyzed by studying experimental water properties measured in protein systems in solution. In particular, proteins in solution modify the structure and the dynamics of the bulk water at the solute-solvent interface. The ordering effects of proteins on hydration water are extended for several angstroms. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on the analysis of the effects of protein-solvent interactions on water protons NMR relaxation parameters. NMR relaxation parameters, especially the nonselective (R₁(NS)) and selective (R₁(SE)) spin-lattice relaxation rates of water protons, are useful for investigating the solvent dynamics at the macromolecule-solvent interfaces as well as the perturbation effects caused by the water-macromolecule interactions on the solvent dynamical properties. In this paper we demonstrate that Nuclear Magnetic Resonance Spectroscopy can be used to determine the dynamical contributions of proteins to the water molecules belonging to their hydration shells.


Integrative Analyses of Genes Associated With Osteoporosis in CD16+ Monocyte.
Osteoporosis is a metabolic bone disease characterized by decreased bone mineral density and abnormal bone quality. Monocytes can secret cytokines for bone resorption, resulting in bone mass loss. However, the mechanism by which monocytes subpopulations lead to osteoporosis remains unclear. The aim of this study was to identify genes associated with osteoporosis in monocytes subsets. Three microarray datasets including GSE7158 (transcription of low/high-peak bone mass), GSE101489 (transcription of CD16+/CD16- monocyte) and GSE93883 (miRNA expression profile of primary osteoporosis) were derived from the Gene Expression Omnibus (GEO) database and analyzed with GEO2R tool to identify differentially expressed genes (DEGs). Functional enrichment was analyzed using Metascape database and GSEA software. STRING was utilized for the Protein-Protein Interaction Network construct. The hub genes were screened out using the Cytoscape software. Related miRNAs were predicted in miRWalk, miRDB, and TargetScan databases. Total 368 DEGs from GSE7158 were screened out, which were mostly enriched in signaling, positive regulation of biological process and immune system process. The hub genes were clustered into two modules by PPI network analysis. We identified 15 overlapping DGEs between GSE101489 and GSE7158 microarray datasets. Moreover, all of them were up-regulated genes in both datasets. Then, nine key genes were screened out from above 15 overlapping DEGs using Cytoscape software. It is a remarkable fact that the nine genes were all in one hub gene module of GSE7158. Additionally, 183 target miRNAs were predicted according to the above nine DEGs. After cross-verification with miRNA express profile dataset for osteoporosis (GSE93883), 12 DEmiRNAs were selected. Finally, a miRNA-mRNA network was constructed with the nine key genes and 12 miRNAs, which were involved in osteoporosis. Our analysis results constructed a gene expression framework in monocyte subsets for osteoporosis. This approach could provide a novel insight into osteoporosis.


Endoscopic rescue of early percutaneous endoscopy gastrostomy tube dislodgement.
Percutaneous endoscopic gastrostomy (PEG) tube placement is one of the most common methods for establishing durable enteral access. Early PEG dislodgement occurs in < 5% of cases but typically prompts urgent surgical intervention to reestablish the gastrocutaneous tract and prevent intra-abdominal sepsis. To date, there is a single case report in the literature where successful endoscopic "rescue" of an early dislodged PEG tube negated the need for operative intervention. Here, we report our experience with a series of endoscopic PEG rescues for early dislodged PEG tubes. A retrospective analysis of cases was reviewed from two institutions. Patients with early PEG dislodgements underwent PEG rescue using a gastroscope and standard Ponsky "Pull" PEG techniques through the original tract. Eleven patients were identified from the database and underwent PEG rescue after early PEG dislodgement. Mean operative time was 68 min, and there were no complications related to PEG rescue. PEG rescue permitted safe re-establishment of the gastrostomy tract while avoiding laparoscopic or open surgical intervention in hemodynamically stable patients. All patients tolerated the procedure well and were able to resume use of the PEG tubes shortly after intervention. Endoscopic rescue represents a feasible noninvasive option for PEG tube replacement following early inadvertent PEG tube dislodgement in appropriate clinical settings.


Interlimb symmetry of traumatic unilateral transtibial amputees wearing two different prosthetic feet in the early rehabilitation stage.
This study evaluated the SACH and the Greissinger Plus prosthetic feet, in terms of the symmetry provided between the lower limbs, in the case of unilateral transtibial amputees 16.3 weeks from the time of limb fitting and 38.9 weeks from surgery. Sagittal plane gait analysis was carried out for nine right-limb traumatic amputees. In all examined cases, the spatial and temporal parameters measured were significantly improved. When the symmetry indexes of the same parameters calculated with three different methods were considered, significant improvement was observed for the hip and ankle ranges of motion and the stance phase period. However, no significant differences were found for the symmetry indexes of the knee range of motion, cadence, and walking speed. In addition, for most spatial parameters, the statistical significance varied considerably among the three methods used for the analysis of symmetry.


Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner.
Nerve growth factor (NGF) is well characterised as an important pro-survival factor in neuronal cells that can inhibit apoptotic cell death upstream of mitochondrial outer membrane permeabilisation. Here we addressed the question of whether NGF can also protect against apoptosis downstream of caspase activation. NGF treatment promoted a rapid reduction in the level of the p17 subunit of active caspase-3 in PC12 cells that had been induced to undergo apoptosis by various cytotoxins. The mechanism involved TrkA-dependent activation of extracellular signal-regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis. Involvement of inhibitor of apoptosis proteins (IAPs) and proteasomal degradation were ruled out. In contrast, inhibition of lysosome function using chloroquine and concanamycin A reversed NGF-induced removal of p17. Moreover, in NGF-treated cells, active caspases were found to be localised to lysosomes. The involvement of macroautophagy and chaperone-mediated autophagy were ruled out. Taken together, these findings suggest an anti-apoptotic mechanism by which NGF induces removal of active caspase-3 in a lysosome-dependent manner.


Leisure, Recreation, and Life Satisfaction: A Longitudinal Study for People With Spinal Cord Injury.
Leisure and recreation (LR) are positively associated with social integration and life satisfaction in people with spinal cord injury (SCI). However, few studies have longitudinally observed long-term changes in LR participation among people with SCI and discussed the association of these activities with social integration and life satisfaction. This study aims to determine for people with SCI, within a 45-year period, the association between mobility and LR participation; the associations between LR participation and social integration and life satisfaction, respectively; and whether the association between LR participation and life satisfaction is mediated by social integration. Growth modeling and linear mixed modeling were employed as the primary data analysis tools to explore longitudinal changes in LR participation, social integration, and life satisfaction. A mediation test was conducted to examine the potential mediation effect of social integration on the relationship between LR participation and life satisfaction. The mobility level, LR participation hours, and social integration of people with SCI decreased gradually during the 45-year period, whereas life satisfaction increased as they lived longer with the injury. LR participation was consistently and positively associated with social integration and life satisfaction of people with SCI. A mediation effect by social integration was observed between LR and life satisfaction. A decline in mobility level was associated with a decrease in LR participation over time for people with SCI. Engaging in LR activities regularly and maintaining a certain level of social interaction are consistently and positively associated with long-term life satisfaction.


European Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS) recommendations for oculoplastic surgeons during the COVID-19 pandemic: a hallenge for the future.
In March 2020, at the outset of the current pandemic, ESOPRS issued detailed advice on the appropriate procedures that practicing oculoplastic surgeons should consider to limit the transmission of COVID-19, with this information updated in April 2020. This paper highlights the threat to training opportunities for future generations of oculoplastic surgeons, adjustments in healthcare delivery, modifications of scientific activity, and the possible role of telemedicine in oculoplastics.


To clip or to coil acutely ruptured intracranial aneurysms: update on the debate.
The purpose of this review is to consider why the International Subarachnoid Aneurysm Trial (ISAT) led to such an uproar, provide a summary of the criticisms of the study and responses from the investigators, and discuss the implications of ISAT. The ISAT was destined for controversy. It pitted two different treatment modalities directly against each other: one a highly evolved, established means for repairing ruptured intracranial aneurysms and the other a radically different, developing approach. The criticisms of the ISAT fall into several categories. They include study site selection, patient selection and the definition of clinical equipoise, relative expertise of the surgeons and interventionists, and the duration and type of follow-up. While some of the criticisms of ISAT reflect unavoidable statistical, design and temporal constraints and thus are of little impact, others are more consequential and revolve around the need for clinical equipoise, and how that was defined across centers. In addition, the question of surgical expertise needs to be addressed. Finally, long-term outcome data are needed. The study was well designed and executed. The published results met the most up-to-date standards for reporting clinical trials. Important questions remain to be answered, including how to define clinical equipoise and the long-term durability of coiling aneurysms.


Immunotoxicity of nanoparticle nTiO2 to a commercial marine bivalve species, Tegillarca granosa.
The increasing production and extensive application of nanoparticles (NPs) inevitably leads to increased release of NPs into the marine environment and therefore poses a potential threat to marine organisms, especially the sessile benthic bivalves. However, the impacts of NPs on the immunity of commercial and ecological important bivalve species, Tegillarca granosa, still remain unknown to date. In addition, the molecular mechanism of the immunotoxicity of NPs still remains unclear in marine invertebrates. Therefore, the immunotoxicity of nTiO2 exposure to T. granosa at environmental realistic concentrations was investigated in the present study. Results obtained showed that the total number, phagocytic activity, and red granulocytes ratio of the haemocytes were significantly reduced after 30 days nTiO2 exposures at the concentrations of 10 and 100 μg/L. Furthermore, the expressions of genes encoding Pattern Recognition Receptors (PPRs) and downstream immune-related molecules were significantly down-regulated by nTiO2 exposures, indicating a reduced sensitivity to pathogen challenges. In conclusion, evident immunotoxicity of nTiO2 to T. granosa at environmental realistic concentrations was detected by the present study. In addition, the gene expression analysis suggests that the PRRs (both TLRs and RIG1 investigated) may be the molecules for NPs recognition in marine invertebrates.


[Trigger mechanisms for cell division in vivo].
A model of stimulating liver regeneration by temporary ligation of selected branches of the hepatic blood vessels was developed in the experiments on rats. For initiating compensatory hypertrophy of the liver it is necessary to compress the portal vessels of the left hepatic lobes up to 20--22 hours, that is until the cells entry into the S-phase. A suggestion was put forward about the differences of stimulation of cell division in the in vivo and in vitro systems.


Higher Dosage of Ciprofloxacin Necessary in Critically Ill Patients: A New Dosing Algorithm Based on Renal Function and Pathogen Susceptibility.
The objective of the present study was to develop a dosing algorithm for ciprofloxacin based on both renal function and pathogen susceptibility in critically ill patients. In this observational prospective multicenter pharmacokinetic study, a total of 39 adult intensive care unit patients receiving ciprofloxacin were included. On two occasions a total of 531 samples of ciprofloxacin were collected. Renal function is a significant covariate on ciprofloxacin clearance. A dose of 400 mg every 12 hours was sufficient to reach the preestablished target of area under the curve (AUC) in relation to the minimum inhibitory concentration (MIC) (AUC/MIC) > 125 in patients with an estimated glomerular filtration rate (eGFR) < 130 mL/min and an infection caused by a pathogen with an MIC ≤ 0.125 mg/L. For patients with infections caused by pathogens with an MIC ≥ 0.5 mg/L and eGFR> 100 mL/min, doses up to 600 mg four times daily or more were estimated to be required. This study provides a new dosing algorithm for ciprofloxacin in critically ill patients. In order to achieve adequate target attainment, the dosing of ciprofloxacin should be based on renal function and the MIC of the causative pathogen. Higher doses than the standard licensed dose are necessary to obtain target attainment for less susceptible pathogens and patients with high renal clearance. In the setting of impaired renal function, a daily dose of 400 mg (which is currently recommended) will not result in adequate target attainment for less susceptible pathogens.


Chronic depression: development and evaluation of the luebeck questionnaire for recording preoperational thinking (LQPT).
A standardized instrument for recording the specific cognitive psychopathology of chronically depressed patients has not yet been developed. Up until now, preoperational thinking of chronically depressed patients has only been described in case studies, or through the external observations of therapists. The aim of this study was to develop and evaluate a standardized self-assessment instrument for measuring preoperational thinking that sufficiently conforms to the quality criteria for test theory. The "Luebeck Questionnaire for Recording Preoperational Thinking (LQPT)" was developed and evaluated using a german sample consisting of 30 episodically depressed, 30 chronically depressed and 30 healthy volunteers. As an initial step the questionnaire was subjected to an item analysis and a final test form was compiled. In a second step, reliability and validity tests were performed. Overall, the results of this study showed that the LQPT is a useful, reliable and valid instrument. The reliability (split-half reliability 0.885; internal consistency 0.901) and the correlations with other instruments for measuring related constructs (control beliefs, interpersonal problems, stress management) proved to be satisfactory. Chronically depressed patients, episodically depressed patients and healthy volunteers could be distinguished from one another in a statistically significant manner (p < 0.001). The questionnaire fulfilled the classical test quality criteria. With the LQPT there is an opportunity to test the theory underlying the CBASP model.


Immune and Cell Therapy in Non-Hodgkin Lymphoma.
The promise of immunotherapy has shone brightly for decades in hematologic malignancies and specifically in non-Hodgkin lymphoma. The last decade has witnessed the emergence of completely novel forms of immunotherapy, including immune checkpoint blockade, bispecific antibodies, and chimeric antigen receptor T cells. These treatments have shown phenomenal, and in some cases possibly curative, successes in various relapsed/refractory lymphomas. This review summarizes the most notable successes and promising findings as well as some of the attendant failures. These treatments will doubtlessly transform the treatment paradigms across many lymphoma subtypes. Yet, only if we can better understand their mechanisms of action, toxicity, and resistance will be able to maximize their therapeutic benefit.


Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.
Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h2 = 0.575, p = 0.010) and the combined APOBEC signatures (h2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10-6 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.


[The characteristics of the glucocorticoid receptors in the striatum of hypertensive rats].
In spontaneously hypertensive rats, the hippocampus has two types of glycocorticoid receptors. In stress, an increase of the receptor binding was found, mainly due to the 2 type receptors. Only one type of receptors was found in the striatum. In stress, the maximal binding of H3-corticosterone with the receptors was enhanced and the dissociation constant increased. The change of the receptors in the striatum can underlie the change in regulation of the hypophyseal-adrenal system function by the feedback mechanism occurring in hypertension in the SHR rats.


ATM regulates the length of individual telomere tracts in Arabidopsis.
Telomeres have the paradoxical ability of protecting linear chromosome ends from DNA damage sensors by using these same proteins as essential components of their maintenance machinery. We have previously shown that the absence of ataxia telangiectasia mutated (ATM), a central regulator of the DNA damage response, accelerates the onset of genome instability in telomerase-deficient Arabidopsis, without increasing the rate of bulk telomere shortening. Here, we examine individual telomere tracts through successive plant generations using both fluorescence situ in hybridization (FISH) and primer extension telomere repeat amplification (PETRA). Unexpectedly, we found that the onset of profound developmental defects and abundant end-to-end chromosome fusions in fifth generation (G(5)) atm tert mutants required the presence of only one critically shortened telomere. Parent progeny analysis revealed that the short telomere arose as a consequence of an unusually large telomere rapid deletion (TRD) event. The most dramatic TRD was detected in atm tert mutants that had undergone meiosis. Notably, in contrast to TRD, alternative lengthening of telomeres (ALT) was suppressed in the absence of ATM. Finally, we show that size differences between telomeres on homologous chromosome ends are greater for atm tert than tert plants. Altogether, these findings suggest a dual role for ATM in regulating telomere size by promoting elongation of short telomeres and by preventing the accumulation of cells that harbor large telomere deletions.


Assessment of Collagen-Based Nanostructured Biomimetic Systems with a Co-Culture of Human Bone-Derived Cells.
Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and other factors, is considered a potential alternative to conventional treatments. Innovative scaffolds need to be tested in in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs), the two main players of bone remodeling, is required to mimic their crosstalk and molecular cooperation. To this aim, two composite materials were developed, based on type I collagen, and containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. The developed nanostructured systems underwent genipin chemical crosslinking and were then tested with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors, for 2-3 weeks. The favorable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of cells, encouraging a further investigation of the developed bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE.


Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.
High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.


A decay of gap junctions in association with cell differentiation of neural retina in chick embryonic development.
Ultrastructural studies of thin-sectioned and freeze-cleaved materials were performed on developing retinal tissues of 3- to 9-day-old chick embryos to clarify the junctional structures between neural retinal cells and between neural retinal cells and cells of the pigmented epithelium. Frequency, size and position of gap junctions in developing neural retina are different at each stage of development. In 3-day-old embryos, some cells adhere to each other by gap junctions immediately below the outer limiting membrane of neural retinae. The size and number of gap junctions increase remarkably during 5-6 days of incubation. In this period of development, well developed gap junctions consisting of subcompartments of intramembrane particles are found between cell surfaces at both the outer limiting membrane region and the deeper portion of the neural retina. Gap junctions disappear thereafter, and at 7-5 days of incubation, small gap junctions are predominant between cell surfaces at the outer limiting membrane region, while the frequency of gap junctions in the deeper portion is very low. At 9 days of incubation, gap junctions are rarely found. Typical gap junctions are always found between neural retinal cells and those of the pigmented epithelium in embryos up to 7-5 days of incubation. Tight junctions are not found in the neural retina or between neural retina and pigmented epithelium throughout the stages examined.


Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression.
Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury.


Activation/Inhibition of mast cells by supra-optimal antigen concentrations.
Mast cells (MCs) are tissue resident cells of hemopoietic origin and are critically involved in allergic diseases. MCs bind IgE by means of their high-affinity receptor for IgE (FcεRI). The FcεRI belongs to a family of multi-chain immune recognition receptors and is activated by cross-linking in response to multivalent antigens (Ags)/allergens. Activation of the FcεRI results in immediate release of preformed granular substances (e.g. histamine, heparin, and proteases), generation of arachidonic acid metabolites, and production of pro-inflammatory cytokines. The FcεRI shows a remarkable, bell-shaped dose-response behavior with weak induction of effector responses at both low and high (so-called supra-optimal) Ag concentrations. This is significantly different from many other receptors, which reach a plateau phase in response to high ligand concentrations. To explain this unusual dose-response behavior of the FcεRI, scientists in the past have drawn parallels to so-called precipitin curves resulting from titration of Ag against a fixed concentration of antibody (Ab) in solution (a.k.a. Heidelberger curves). Thus, for high, supra-optimal Ag concentrations one could assume that every IgE-bound FcεRI formed a monovalent complex with "its own Ag", thus resulting in marginal induction of effector functions due to absence of receptor cross-linking. However, this was never proven to be the case. More recently, careful studies of FcεRI activation and signaling events in MCs in response to supra-optimal Ag concentrations have suggested a molecular explanation for the descending part of this bell-shaped curve. It is obvious now that extensive FcεRI/IgE/Ag clusters are formed and inhibitory molecules and signalosomes are engaged in response to supra-optimal cross-linking (amongst them the Src family kinase Lyn and the inositol-5'-phosphatase SHIP1) and they actively down-regulate MC effector responses. Thus, the analysis of MC signaling triggered by supra-optimal crosslinking holds great potential for identifying novel targets for pharmacologic therapeutic intervention to benefit patients with acute and chronic allergic diseases.


Children's vision--a 20/20 outlook.
Twenty years ago, A. M. Skeffington, O.D., talked about the "uniqueness" of optometry which included prevention, remediation and enhancement. Fifteen years ago, Arnold Gesell, M.D., urged optometry to pay attention to the preschool years and to examine and supervise (with optometric expertise) the vision of these children and to learn to identify those children who would present difficulties in learning. At the same time, Darell Boyd Harmon, Ph.D., suggested that optometry "gear up" for an expected avalanche of visually-related learning problems. Optometry did listen and learn, the avalanche is here and developmental optometry has prospered. This paper briefly explores some of the long and short-range benefits of vision therapy.


Differentiation of superficial thrombophlebitis from lymphangitis by doppler ultrasound.
Of 61 patients examined by Doppler ultrasound, only 23 were found to have superficial venous thrombosis. The remaining 38 patients were considered to have lymphangitis or cellulitis. An algorithm of diagnostic and therapeutic pathways has been developed for the management of the patient who has suspected superficial thrombophlebitis.


In Vitro and Ex Vivo Analysis of Collagen Foams for Soft and Hard Tissue Regeneration.
The aim of this study was the conception, production, material analysis and cytocompatibility analysis of a new collagen foam for medical applications. After the innovative production of various collagen sponges from bovine sources, the foams were analyzed ex vivo in terms of their structure (including pore size) and in vitro in terms of cytocompatibility according to EN ISO 10993-5/-12. In vitro, the collagen foams were compared with the established soft and hard tissue materials cerabone and Jason membrane (both botiss biomaterials GmbH, Zossen, Germany). Collagen foams with different compositions were successfully produced from bovine sources. Ex vivo, the foams showed a stable and long-lasting primary structure quality with a bubble area of 1,000 to 2,000 μm2 In vitro, all foams showed sufficient cytocompatibility. Collagen sponges represent a promising material for hard and soft tissue regeneration. Future studies could focus on integrating and investigating different additives in the foams.


Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up.
To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ). A retrospective study One consultant-led colposcopy clinic at Leicester Royal Infirmary Three hundred and ninety-four women referred consecutively to the colposcopy clinic between 1991 and 1992. The histological recurrence rate of CIN, length of cytological follow up following treatment related to degree of completeness of excision at initial treatment. Three hundred and twenty-two women had complete cytological or histological follow up. The mean length of follow up was 73 months with a mean number of six smears. Women with incomplete excision of CIN had a significantly higher risk of recurrent CIN (relative risk 8.23) occurring in a significantly shorter time compared with women with complete excision. This study demonstrates that large loop excision of transformation zone is successful in over 95% of cases. Cytological surveillance is satisfactory for follow up of women who have complete excision of CIN. Women with incomplete excision of CIN at initial LLETZ remain at significant risk of developing further CIN and long term colposcopic and cytological follow up is necessary.


Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants.
Fortification of breast milk is an accepted practice for feeding very low birth weight infants, however, fixed dosage enhancement does not address variations in native breast milk. This could lead to deficiencies in calories and macronutrients. We therefore established the infrastructure for target fortification in breast milk by measuring and adjusting fat, protein, and carbohydrate content daily. We analyzed nutrient intake, growth, and safety variables. Each 12-hour batch of breast milk was analyzed using near-infrared spectroscopy. Macronutrients were individually added to routine fortification to achieve final contents for fat (4.4 g), protein (3 g), and carbohydrates (8.8 g) (per 100 mL). Fully breast milk fed healthy very low birth weight infants (<32 weeks) were fed the fortified breast milk for at least 3 weeks. Matched pair analysis of 20 infants fed routinely fortified breast milk was performed using birth weight, gestational age, and postnatal age. All 650 pooled breast milk samples required at least 1 macronutrient adjusted. On average, 0.3 ± 0.4 g of fat, 0.7 ± 0.2 g of protein, and 1.2 ± 0.2 g of carbohydrate were added. Biochemistry was normal in the 10 target fortified infants (birth weight: 860 ± 309 g, 26.3 ± 1.6 weeks gestational age); weight gain was 19.9 ± 2.7 g/kg/d; and milk intake was 147 ± 5 mL/kg/d (131 ± 16 kcal/kg/d). Osmolality of fortified breast milk was 436 ± 13 mOsmol/kg. Matched pair analysis of infants indicated a higher milk intake (155 ± 5 mL/kg/d) but similar weight gain (19.7 ± 3.3 g/kg/d). No adverse event was observed. The linear relationship between milk intake and weight gain observed in study babies but not seen in matched controls may be related to the variable composition of breast milk. Daily target fortification can be safely implemented in clinical routine and may improve growth.


International surgery and the University of Connecticut experience: lessons from a short-term surgical mission.
Surgery is gradually gaining recognition within the international public health community as an essential component to sustainable improvements in health care in resource-poor areas. In this article, we document the University of Connecticut experience with international surgical missions, and we offer avenues for optimization of these efforts. A one-week elective trip to San José de Chiquitos, Bolivia to provide essential general surgical care to a rural, underserved population. We collaborated with local health-care personnel in both intraoperative and perioperative care. Forty-one major cases were performed over a week-long period. The majority of cases were open cholecystectomy, but a variety of emergency and elective surgical cases were performed. There were no postoperative complications over a three-month follow-up. International surgical trips are an essential component of public health initiatives abroad; surgery can provide a vital role in the health care of underserved populations. Few domestic programs have formal international surgical curricula within the residency program; we offer beneficial results based on a short-term model. Future studies should focus on the development of sustainable, surgical programs that focus on education of local health-care personnel in underserved regions.


Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.
Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV. The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique. Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm. Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.


Recovery of spectral reflectances of objects being imaged without prior knowledge.
Prior knowledge of the noise present in a color image acquisition device is very important in estimating colorimetric values or in recovering the spectral reflectances of pixels of objects being imaged, since these values are greatly influenced by the noise. In this paper, a new model is proposed for the determination of the noise variance of a multispectral color image acquisition system and experimental results to demonstrate its accuracy are presented. It is demonstrated that the noise variance of an actual multispectral color image acquisition system computed by the proposal agrees fairly well with the variance which minimizes the mean-square error of the recovered reflectances by the Wiener filter. As an application of the proposal, it is shown that spectral reflectances of an art painting are recovered accurately by the use of sensor responses without prior knowledge of objects being imaged and noise present in an image acquisition system.


SF-36 Shows Increased Quality of Life Following Complete Reduction of Postmastectomy Lymphedema with Liposuction.
Abstracts Background: Arm lymphedema after breast cancer surgery affects women both from physical and psychological points of view. Lymphedema leads to adipose tissue deposition. Liposuction and controlled compression therapy (CCT) reduces the lymphedema completely. Sixty female patients with arm lymphedema were followed for a 1-year period after surgery. The 36-item short-form health survey (SF-36) was used to assess health-related quality of life (HRQoL). Patients completed the SF-36 questionnaire before liposuction, and after 1, 3, 6, and 12 months. Preoperative excess arm volume was 1365 ± 73 mL. Complete reduction was achieved after 3 months and was sustained during follow-up. The adipose tissue volume removed at surgery was 1373 ± 56 mL. One month after liposuction, better scores were found in mental health. After 3 months, an increase in physical functioning, bodily pain, and vitality was detected. After 1 year, an increase was also seen for social functioning. The physical component score was higher at 3 months and thereafter, while the mental component score was improved at 3 and 12 months. Compared with SF-36 norm data for the Swedish population, only physical functioning showed lower values than the norm at baseline. After liposuction, general health, bodily pain, vitality, mental health, and social functioning showed higher values at various time points. Liposuction of arm lymphedema in combination with CCT improves patients HRQoL as measured with SF-36. The treatment seems to target and improve both the physical and mental health domains.


Multiscale modeling and data integration in the virtual physiological rat project.
It has become increasingly evident that the descriptions of many complex diseases are only possible by taking into account multiple influences at different physiological scales. To do this with computational models often requires the integration of several models that have overlapping scales (genes to molecules, molecules to cells, cells to tissues). The Virtual Physiological Rat (VPR) Project, a National Institute of General Medical Sciences (NIGMS) funded National Center of Systems Biology, is tasked with mechanistically describing several complex diseases and is therefore identifying methods to facilitate the process of model integration across physiological scales. In addition, the VPR has a considerable experimental component and the resultant data must be integrated into these composite multiscale models and made available to the research community. A perspective of the current state of the art in model integration and sharing along with archiving of experimental data will be presented here in the context of multiscale physiological models. It was found that current ontological, model and data repository resources and integrative software tools are sufficient to create composite models from separate existing models and the example composite model developed here exhibits emergent behavior not predicted by the separate models.


[Biological aspects of radiation in nuclear medicine].
Radiotherapy with unsealed radionuclides differs from external radiotherapy with regard to the radiation quality and energy range, the regional dose uniformity and the time course of irradiation regimen. External radiotherapy is planned precisely and can be applied to a target volume independently from blood flow during a course of irradiation fractions. In contrary, administered radiopharmaceuticals distribute according to their pharmacokinetic properties and generate a continuous irradiation corresponding to the effective halflife. The resulting dose rates are approximately 1Gy/min and 1Gy/h, respectively. The biokinetics of radiopharmaceuticals involves cellular accumulation and retention with highly variable affinity to specific organs that can be modulated as well. A remarkable dose gradient is found at the edge of volumes with enhanced uptake. The biological effect of an irradiation with decreasing intensity can be compared with the radiation effect caused by conventional fractionation with 2 Gy a day in external beam therapy by means of the linear-quadratic model. However, the experimental validation of this translation is still under investigation. Radionuclide therapy is usually performed in several cycles some month apart. This procedure fails to meet external radiotherapy. The vision of a combined external-internal radiotherapy requires efforts for a common dosimetry approach both in vitro and in vivo with a physical and biological verification of the results.


Combination of on-line CE assay with MS detection for the study of drug metabolism by cytochromes P450.
A new CE-MS method with enzymatic reaction inside the capillary was developed for the study of drug metabolism by cytochromes P450. This automated method, based on the transverse diffusion of laminar flow profiles methodology, is comprised of the injection of substrates and enzyme, their mixing, incubation, and separation of the reaction products, all performed by CE, and their detection, identification, and quantification by MS. The developed and validated method was finally used to conduct a kinetic study of cytochrome P450 isoform 2C9 or human liver microsomes with diclofenac in order to demonstrate its practical functionality. All the estimated kinetic values--apparent Michaelis constants and apparent maximum reaction velocities were in agreement with literature data obtained using other techniques. In addition, the consumption of reactants was in the tens of nL per analysis. The method's usability was further demonstrated on tolbutamide, the other probe substrate of cytochrome P450 isoform 2C9. As a result, the method is conceptually applicable for the screening of any other cytochrome P450 isoform and its substrates and inhibitors after adapting the incubation and separation conditions.


Suprapatellar pouch ganglion cyst managed with arthroscopic excision: a case report.
This report highlights the first known case of an intra-articular ganglion cyst of the suprapatellar pouch. The patient presented with insidious-onset medial knee pain, swelling, and progressive dysfunction. Initial imaging was negative for pathology. More extensive thigh imaging led to the diagnosis. The patient was treated successfully with arthroscopic excision and was symptom-free at final follow-up.


Neutrophils mediate immunopathology and negatively regulate protective immune responses during fatal bacterial infection-induced toxic shock.
Ehrlichia chaffeensis is an obligate intracellular bacterium that infects primarily monocytes and macrophages and causes potentially fatal human monocytic ehrlichiosis (HME) that mimics toxic-shock-like syndrome in immunocompetent hosts. Early recruitment of neutrophils to the sites of infection is critical for the control of bacterial infection and inflammatory responses. We recently observed rapid and sustained neutrophil recruitment at a primary site of infection (peritoneum) following lethal murine ehrlichial infection compared to innocuous ehrlichial infection. We examined here the contribution of neutrophils to protective immunity or immunopathology during infection with monocytic Ehrlichia. Unexpectedly, depletion of neutrophils from lethally infected mice enhanced bacterial elimination, decreased immune-mediated pathology, and prolonged survival. Furthermore, compared to lethally infected sham controls, neutrophil depletion in infected mice resulted in amelioration of pathogenic responses, as evidenced by a decreased number of tumor necrosis factor alpha (TNF-α)-producing CD8(+) T cells, which is known to mediate immunopathology and toxic shock in a murine model of fatal ehrlichiosis. Although neutrophil depletion did not influence the number of CD4(+) Th1 cells and NKT cells producing gamma interferon (IFN-γ), it increased the ratio of IFN-γ- to IL-10-producing NKT cells as well as the ratio of IFN-γ to interleukin 10 (IL-10) transcripts in the liver. This may ameliorate the net suppressive effect of IL-10 on IFN-γ-mediated activation of infected macrophages and thus may account for the enhanced bacterial elimination. Finally, transcriptional analysis of gene expression in the liver indicated that neutrophils contribute to overproduction of cytokines and chemokines during fatal ehrlichiosis. In conclusion, these results revealed an unexpected role of neutrophils in supporting bacterial replication indirectly and promoting immunopathology during severe infection with an intracellular bacterium.


Patterns of gastric myoelectrical activity in human subjects of different ages.
The aim of this study was to investigate the developmental change of gastric myoelectrical activity in humans. Five groups of healthy subjects were studied, including 10 preterm newborns, 8 full-term newborns, 8 full-term infants (ages 2-6 mo), 9 children (ages 4-11 yr), and 9 adults. Gastric myoelectrical activity was recorded using surface electrogastrography for 30 min before and 30 min after a test meal in each subject. Spectral analysis methods were applied to compute the parameters of the electrogastrogram (EGG). The results showed that the percentage of 2- to-4-cycles/min (cpm) slow waves was 26.6 +/- 3.9% in the preterm newborns, 30.0 +/- 4.0% in full-term newborns, 70 +/- 6.1% in 2- to 6-mo-old infants (P < 0.001 compared with newborns), 84.6 +/- 3.2% in 4- to 11-yr-old children (P < 0.03 compared with infants), and 88.9 +/- 2.2% in the adults (P > 0.05 compared with children). In conclusion, gastric slow waves are absent at birth, and there is a maturing process after birth. Age-matched controls are necessary for the interpretation of EGG data from neonates and infants, whereas EGG data in children are the same as in adults.


Management strategy of mycobacterial cervical lymphadenitis.
The objectives of this study were to investigate the typical clinical presentation, diagnosis and treatment of mycobacterial cervical lymphadenitis (MCL). Medical records of 87 patients who were treated for MCL were retrospectively reviewed. Definitive diagnosis of MCL was made when a neck mass persisted for several weeks or months and one or more of the following was obtained: (1) positive mycobacterial cultures from biopsy material; (2) Positive mycobacterial staining of biopsy material; (3) Granulomatous inflammation and caseating necrosis on histopathological examination of biopsy material. Clinical findings were reviewed prior to treatment. The treatment included standard antituberculous medications followed by surgery in which either total excision or selective nodal dissection of the cervical lump was made. Follow-up results are presented. The chief complaint was a cervical mass that was localized mostly to the posterior cervical or submandibular regions. A fistula formation was encountered in 11.5 per cent. All patients recovered from MCL by combined antituberculous drug and surgical treatments. Clinical presentation of the disease and histopathological assessment are important in the diagnosis of MCL as well as in the differential diagnosis of tuberculous and nontuberculous MCL. Utilizing the combined medical and surgical treatment options, both tuberculous and non-tuberculous cervical adenitis can be treated successfully.


Assessment of wound infiltration with bupivacaine in women undergoing day-case gynecological laparoscopy.
The effectiveness of local anesthetic wound infiltration for treatment of postoperative pain appears to be variable and partly dependent on the surgical procedure. Although evidence was lacking, it was common practice at our institution to infiltrate the trocar wound of patients undergoing day-case laparoscopic procedures with long acting local anesthetic agents. The aim of this study was to investigate the analgesic efficacy, and the influence of the timing, of local anesthetic infiltration into surgical wounds for day-case diagnostic gynecological laparoscopy. A double-blind, randomized trial was conducted on 100 women having general anesthesia for day-case gynecological laparoscopy. Ninety-two patients who had been randomized to 1 of 4 groups for trocar wound infiltration with 30 mL of 0.25% bupivacaine or saline either before or after surgery completed the study. Incisional pain, pain on pressing the umbilicus, severity of nausea, and patient satisfaction with anesthetic technique were all assessed postoperatively until discharge and on the following day through a telephone interview. A P value of <.05 was considered significant. There was no difference between groups in the mean pain scores or analgesic requirements for incisional pain, pain on pressing firmly on the umbilicus, or for patient satisfaction. There was a trend for those patients who had received bupivacaine to use less postoperative morphine (P =.079). Wound infiltration with local anaesthetic did not significantly reduce pain or opioid requirement after gynecological laparoscopy.


Effects of alcohol retail privatization on excessive alcohol consumption and related harms: a community guide systematic review.
Excessive alcohol consumption is the third-leading cause of preventable death in the U.S. This systematic review is one in a series exploring effectiveness of interventions to reduce alcohol-related harms. The focus of this review was on studies evaluating the effects of the privatization of alcohol retail sales on excessive alcohol consumption and related harms. Using Community Guide methods for conducting systematic reviews, a systematic search was conducted in multiple databases up to December 2010. Reference lists of acquired articles and review papers were also scanned for additional studies. A total of 17 studies assessed the impact of privatizing retail alcohol sales on the per capita alcohol consumption, a well-established proxy for excessive alcohol consumption; 9 of these studies also examined the effects of privatization on the per capita consumption of alcoholic beverages that were not privatized. One cohort study in Finland assessed the impact of privatizing the sales of medium-strength beer (MSB) on self-reported alcohol consumption. One study in Sweden assessed the impact of re-monopolizing the sale of MSB on alcohol-related harms. Across the 17 studies, there was a 44.4% median increase in the per capita sales of privatized beverages in locations that privatized retail alcohol sales (interquartile interval: 4.5% to 122.5%). During the same time period, sales of nonprivatized alcoholic beverages decreased by a median of 2.2% (interquartile interval: -6.6% to -0.1%). Privatizing the sale of MSB in Finland was associated with a mean increase in alcohol consumption of 1.7 liters of pure alcohol per person per year. Re-monopolization of the sale of MSB in Sweden was associated with a general reduction in alcohol-related harms. According to Community Guide rules of evidence, there is strong evidence that privatization of retail alcohol sales leads to increases in excessive alcohol consumption.


[Epidemiological study and development of dental caries in Madrid students].
It has been done an epidemiologic study about dental caries prevalence in a school population in Madrid. We have studied 3,608 schoolchildren. Total caries prevalence was 53.4%, according other authors. Caries is more frequent between ten years children. We also observed low prevalence in the third year of the study.


Physicians' preferences for information sources: a meta-analytic study.
Identification of the resources physicians use to acquire information for clinical practice and medical research is an important area of research for health sciences librarianship and medical practice. During the past twenty years several studies have addressed questions about physicians' preferences for information sources, but generalization from the results of these studies has been hampered by limited sampling, diverse methods, and varied reportorial formats. Meta-analysis provides a method for reducing these limits. Using a meta-analytic procedure, this study reviews twelve studies published between 1978 and 1992, categorizes and ranks the physicians' preferred information sources reported in each study, then aggregates and counts the frequencies of the top six preferences, as well as the associated first and second preferences, for all the study populations or their strata. The results indicate that physicians prefer to obtain information from journals and books, but also that they often consult colleagues to get answers to clinical and research questions. The implications of these findings for health sciences librarianship are briefly discussed.


Sensory processing patterns of young adults with preterm birth history.
This study aimed to evaluate the sensory processing abilities of young adults with a history of preterm birth and the factors affecting these abilities. Thirty-seven young adults with preterm birth history were included. After recording their sociodemographic data, sensory processing functions were evaluated using the Adolescent/Adult Sensory Profile. The participants' data were compared to normative samples. Mean score was 43.51 ± 8.29 for sensory sensitivity, 44.45 ± 9.19 for sensation avoiding, 33.43 ± 8.45 for low registration, and 47.97 ± 9.91 for sensation seeking. Compared to normative samples, 78% of participants in sensation avoiding quadrant, 62% of participants in sensory sensitivity quadrant, 40% of participants in low registration quadrant and sensation seeking quadrant had atypical scores. When sensory profile scores were analysed according to mode of birth, percentages of typical sensory sensitivity and sensation avoiding were low in both the normal vaginal and caesarean delivery subgroups. When analysed by gestational age at birth, ratios of abnormality in sensation avoiding were similar between individuals with very early, early, and late preterm delivery history. Statistically significant difference was found in low registration and sensation avoiding quadrants according to mode of birth (p < .05). There were no statistically significant sex-based and gestational age at birth differences in any of the four quadrants of the sensory profile in the preterm group (p > .05). These results showed that young adults with preterm birth history have differences in sensory processing compared to the general population and should be evaluated for sensory processing patterns.


[A Long Stream: The Historical Influence of Peking Union Medical College on the Development of Modern Nursing Education in Taiwan].
The faculty of Peiping Union Medical College (PUMC) formatively influenced the development of modern nursing in Taiwan. PUMC, which retreated with the national government to Taiwan from Mainland China in 1949, was initially established earlier in that century by enthusiastic medical missionaries and later reformed by the Rockefeller Foundation. After relocating to Taiwan, PUMC teachers and graduates have provided critical leadership in disseminating modern nursing education in Taiwan and in integrating public health and clinical services to establish a solid foundation for Taiwanese nursing education. To highlight the significant contributions of PUMC alumni in Taiwan, this article explores three dimensions as follows: 1) Establishing the foundation of modern nursing education in Taiwan; 2) Channeling aids from the United States and the international communities to improve nursing education; and 3) Raising the international profile and influence of the Taiwan nursing society. In celebration of the centennial anniversary of PUMC, we encourage in the spirit of PUMC congeniality greater Cross-Strait collaboration among elite professionals in order to further advance PUMC leadership in Asian medical education and cultural enlightenment.


Electron localizability indicators from spinor wavefunctions.
For the fully relativistic 4-component many-electron wavefunction six flavors of electron localizability indicators (ELI) have been proposed. Their counterparts, suitable for the application to the 2-component wavefunctions, have been also derived. Six proposed indicators have been tested on Ar and Rn atoms and one of them, the ELI-D for spatially antisymmetrized electron pairs, has been found to reveal atomic shell structures at quantitative level. Shell structures of all the atoms of periods 4-7 of the periodic table have been obtained using this indicator and compared with these obtained from the nonrelativistic limit calculations as well as from scalar-relativistic (zero-order regular approximation) calculations.


Cholesterol and the interaction of proteins with membrane domains.
Cholesterol is not uniformly distributed in biological membranes. One of the factors influencing the formation of cholesterol-rich domains in membranes is the unequal lateral distribution of proteins in membranes. Certain proteins are found in cholesterol-rich domains. In some of these cases, it is as a consequence of the proteins interacting directly with cholesterol. There are several structural features of a protein that result in the protein preferentially associating with cholesterol-rich domains. One of the best documented of these is certain types of lipidations. In addition, however, there are segments of a protein that can preferentially sequester cholesterol. We discuss two examples of these cholesterol-recognition elements: the cholesterol recognition/interaction amino acid consensus (CRAC) domain and the sterol-sensing domain (SSD). The requirements for a CRAC motif are quite flexible and predict that a large number of sequences could recognize cholesterol. There are, however, certain proteins that are known to interact with cholesterol-rich domains of cell membranes that have CRAC motifs, and synthetic peptides corresponding to these segments also promote the formation of cholesterol-rich domains. Modeling studies have provided a rationale for certain requirements of the CRAC motif. The SSD is a larger protein segment comprising five transmembrane domains. The amino acid sequence YIYF is found in several SSD and in certain other proteins for which there is evidence that they interact with cholesterol-rich domains. The CRAC sequences as well as YIYF are generally found adjacent to a transmembrane helical segment. These regions appear to have a strong influence of the localization of certain proteins into domains in biological membranes. In addition to the SSD, there is also a domain found in soluble proteins, the START domain, that binds lipids. Certain proteins with START domains specifically bind cholesterol and are believed to function in intracellular cholesterol transport. One of these proteins is StAR-D1, that also has a mitochondrial targeting sequence and plays an important role in delivering cholesterol to the mitochondria of steroidogenic cells.


Direct sequential C-H iodination/organoyl-thiolation for the benzenoid A-ring modification of quinonoid deactivated systems: a new protocol for potent trypanocidal quinones.
We report a sequential C-H iodination/organoyl-thiolation of naphthoquinones and their relevant trypanocidal activity. Under a combination of AgSR with a copper source, sulfur-substituted benzenoid quinones were prepared in high yields (generally >90%). This provides an efficient and general method for preparing A-ring modified naphthoquinoidal systems, recognized as a challenge in quinone chemistry.


Condom use self-efficacy centered on sexual experience, cannabis, and CBD use among college students.
The goal of this study was to understand how condom use self-efficacy varies based on sexual experience, cannabis and CBD use. A cross-sectional survey was implemented through Qualtrics. A total of 455 undergraduate students were surveyed at a large U.S. northeastern university. Findings suggested that sexual experience itself and sexual experience with cannabis and CBD are associated with a person's condom use self-efficacy. Precisely, non-sexually active and cannabis or CBD nonusers perceived themselves as less efficacious in their future use of condoms compared with sexually active adolescents. Implications for health interventions are discussed, such as the importance of giving attention to non-sexually active adolescents and strengthening their condom use self- efficacy. It is critical to promote healthy sexual behaviors among future sexually active college students and reinforce healthy sexual behaviors among sexually active adolescents.


2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group.
In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology. A literature review (1990-2007) on CVC-associated thrombosis was carried out. The guidelines were developed on the basis of the corresponding levels of evidence derived from analysis of the 36 of 175 publications selected. They were then peer reviewed by 65 independent experts. For the prevention of CVC-associated thrombosis, the distal tip of the CVC should be placed at the junction between the superior cava vein and right atrium; anticoagulants are not recommended. Treatment of CVC-associated thrombosis should be based on the prolonged use of low-molecular weight heparins. Maintenance of the catheter is justified if it is mandatory, functional, in the right position, and not infected, with a favorable clinical evolution under close monitoring; anticoagulant treatment should then be continued as long as the catheter is present. Several rigorous studies do not support the use of anticoagulants for the prevention of CVC-associated thrombosis. Treatment of CVC-associated thrombosis relies on the same principles as those applied in the treatment of established thrombosis in cancer patients.


[Results of 30 years' surgical treatment of acquired defects and diseases of the heart].
A total of 11085 patients have been operated on for rheumatic heart diseases over thirty years, 85.4% of those, for mitral stenosis or its relapse, using the "closed" method (total mortality was 2.7%). In recent years, the mortality rate has dropped to 1.5% in that group of patients. Prevention of heart failure and thromboembolic complications still are the principal problem of mitral commissurotomy. Traumatic regurgitation was seen in 2%. The operation was performed under extracorporeal circulation in 6.2% of patients. Mortality, associated with mitral prosthesis implantation, has decreased threefold (to 10.8%) over 15 years. A total of 131 patients have been operated on for constrictive pericarditis, the mortality rate was 10.7%. Primary implantation of electric pacemaker for complete transverse heart block has been performed in 196 patients, and the generator was replaced in 143 patients.


Glycyl-glutamine-enriched long-term total parenteral nutrition attenuates bacterial translocation following small bowel transplantation in the pig.
Improvements in immunosuppression, operative procedure, and posttransplant management have made clinical small bowel transplantation (SBT) feasible. Ischemia and reperfusion injury, total parenteral nutrition (TPN), and devoidment of enteral feeding lead to graft atrophy, gut barrier dysfunction, and bacterial translocation. Glutamine (Gln) is the principal fuel for the enterocyte. The influence of Gln dipeptide-supplemented TPN, especially long-term TPN, on intestinal graft permeability and bacterial translocation is not clear following SBT in the large animal model. Therefore, we studied the effect of glutamine dipeptide, glycyl-glutamine (Gly-Gln), on bacterial translocation following SBT in the pig, which has a physiology similar to humans. The outbred pigs underwent segmental small bowel autotransplantation and were divided into two groups. In the STPN group (n = 5), the animal received standard TPN devoid of Gly-Gln for 28 days. In the GTPN group (n = 5), the animal received isonitrogenous (0.3 g/kg.day) and isocaloric (33 kcal/kg.day) TPN solution with 2% Gly-Gln for 28 days. At the end of the experiment, Gly-Gln-enriched TPN could maintain the plasma Gln level, graft mucosal Gln and protein concentrations, and skeletal muscle Gln and protein concentrations. Gly-Gln-enriched TPN significantly decreased the bacterial number of mesenteric lymph nodes in the liver and spleen and intestinal permeability to 99mTc-DTPA. There were no significant differences in body weight gain. The Gly-Gln-enriched long-term TPN may maintain the plasma Gln level, mucosal and muscle Gln, and protein concentrations and attenuate the intestinal permeability to 99mTc-DTPA and bacterial translocation following small bowel transplantation in the pig.


The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.
Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.


DJ-1 Mutations are Rare in a Swedish Parkinson Cohort.
Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson's disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide.