Event-related brain potentials in selective response.
Event-related potentials were recorded during performance of a simple reaction task and two selective response tasks differing in the intensity of the non-key stimulus. Known differences in reaction between these tasks were confirmed, but there were no corresponding differences in amplitude of the slow potential shift which develops in the EEG in anticipation of the imperative signal. Since this anticipatory potential is not affected by event uncertainty, it seems to be related to motor preparation rather than to expectancy. Performance differences between simple and selective response tasks appear to depend not upon differential preparation, but upon selective processing of the imperative signal, which is reflected in the N120 component of the visual evoked response to that signal.


How Safe is the Use of Intrathecal Fluorescein? An Experimental Study.
To investigate the effects of fluorescein-sodium on neural tissues. Twenty-one Wistar rats were randomly divided into three experimental groups: control (group 1) and fluorescein-sodium groups with different doses (groups 2 and 3). In the control group, craniectomy following with durotomy was performed with the help of a loupe microscope, and a dry sponge was overlayed to the brain tissue. In the study groups, the open dura was covered with a sponge soaked with 0.02 mg (group 2) and with 0.2 mg (group 3) fluorescein sodium following craniectomy. Three weeks postoperatively, rats were sacrificed for the histopathologic evaluations. Fluorescein-induced apoptosis occurs in a dose-dependent manner in rats' neurons. It was determined that neuron and neuroglial cell TUNEL staining was statistically different among the three groups (p < 0.001). Our results indicated that fluorescein induces apoptosis, resulting in increased nuclear factor kappa beta (NF-kβ) expression in a dose-dependent manner. Fluorescein sodium is used frequently during surgery for CSF fistulas. However, information in the literature about its safety is insufficient. Our study holds promise for the development of new studies on the reliability of this agent.


Dietary intervention for children and adolescents with familial hypercholesterolaemia.
Familial hypercholesterolaemia (FH) is a frequent genetic disorder characterised by high plasma levels of total and LDL-cholesterol and premature atherosclerosis. If left untreated, affected subjects have a high risk of cardiovascular disease, as they are exposed to very high levels of LDL-cholesterol from birth. Healthy dietary habits and lifestyle are the first treatment option and, if started from childhood, represent a milestone in the prevention of atherosclerotic disease, both as a starting point and in combination with drug therapy. In this work, based on the main consensus documents available so far, we have evaluated the most up-to-date indications of the dietetic-nutritional intervention for the treatment of FH, delving into the peculiar aspects of the diet of the child/adolescent affected by FH. After an analysis of the macro- and micronutrients and the most common dietary patterns currently recommended, we highlighted some practical aspects, some frequent errors and some risks we could fall into when dealing with paediatric nutritional treatment. In conclusion, the dietary intervention for the child/adolescent with FH is a complex task, that should be individualised and tailored taking into account, first of all, the nutritional adequacy for growth and development, but also the multiple aspects linked to the child/adolescent's age, tastes and preferences, the family they belong to, the socio-economic context and the Country they live in.


Evidence of gold-gold intra- and intermolecular interactions gained by laser desorption/ionisation and fast atom bombardment mass spectrometry in the study of some gold(I) coordination compounds
The mass spectrometric behaviour of some two-coordinated linear gold(I) complexes has been studied by fast atom bombardment (FAB) and laser desorption/ionisation (LDI) methods. The results obtained demonstrate some interesting aspects of Au-Au interactions. The detection under FAB conditions of Au(n)(+) clusters, in particular of Au(3)(+) species, can be rationalised by the presence of significant intramolecular Au-Au interactions, while the formation under LDI conditions of Au(n)(+) clusters can be considered indicative of Au(ellipsis)Au intermolecular interactions present in the solid state. Copyright 2000 John Wiley & Sons, Ltd.


Searching for cancer-related information online: unintended retrieval of complementary and alternative medicine information.
The Web is an important source of health information for consumers. Use of complementary and alternative medicine (CAM) is also increasing. Therefore, we studied the likelihood that consumers will incidentally encounter CAM information while searching the Web and the factors that influence retrieval of CAM information. We evaluated results retrieved by 10 cancer-related searches on six common search engines. Of 1121 search results, 16.2% displayed CAM information. Sponsored (i.e., paid) results were more likely to display CAM information than non-sponsored results (38% versus 7.5%, p < 0.001). In Overture and Google, sponsored results accounted for 51% and 39% of results on the first page. These search engines also retrieved more CAM web pages. Search engines distinguished sponsored and non-sponsored results, but disclosure statements describing the differences were confusing. Cancer type used as the search keyword did not influence the number of CAM web pages retrieved. However, synonyms of cancer differed in their retrieval of CAM web pages (p < 0.001). Consistent with prior studies of Web search engine overlap, we found that 28% of CAM results were retrieved by two or more search engines. Clinicians should help consumers recognize sponsored results and encourage search engines to clearly explain sponsored results.


Phase 1 Trial Evaluating Vorinostat Plus Bortezomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma.
Bortezomib plus lenalidomide and dexamethasone (VRD) is a standard induction therapy for newly diagnosed multiple myeloma (NDMM) patients. Given preclinical and clinical data suggesting the synergistic activity of the histone deacetylase inhibitor vorinostat with both bortezomib and lenalidomide for the treatment of multiple myeloma, we hypothesized that adding vorinostat to VRD (R2V2) would increase the rate and the quality of responses to induction treatment. Here we report the results of a phase 1 trial (NCT01038388) evaluating R2V2 as up-front treatment for NDMM patients. R2V2 was tested as induction therapy in a dose-escalation phase 1 study in 30 NDMM patients deemed eligible for autologous stem-cell transplantation. Treatment consisted of 4 induction cycles with R2V2, followed by either autologous stem-cell transplantation or 4 additional R2V2 cycles and lenalidomide maintenance therapy. The maximum tolerated dose of vorinostat was 200 mg daily. The most common adverse events were gastrointestinal (87%), fatigue and peripheral neuropathy (60%), and thrombocytopenia (33%). R2V2 induced an objective response in 96% of patients, with 48% obtaining at least a complete remission. Median progression-free survival was 52 months, with 77% of patients alive at 5 years. R2V2 as induction treatment for NDMM patients resulted in remarkable response rates at the cost of increased toxicity.


The complete amino acid sequence of human complex-forming glycoprotein heterogeneous in charge (protein HC) from one individual.
The complete amino acid sequence of the single polypeptide chain of human complex-forming glycoprotein heterogeneous in charge (protein HC) isolated from a single individual is reported with the supporting data. The primary structure was determined by automatic degradation of the intact chain and of fragments obtained by chemical and enzymatic degradations of the native or reduced and S-carboxymethylated protein. The polypeptide chain of protein HC contained 182 amino acid residues with a calculated molecular weight of 20,621. No amino acid sequence variability was found and such variability can therefore not explain the great charge heterogeneity of protein HC in a single individual. The amino acid sequence of protein HC was nearly identical to the one reported for human alpha 1-microglobulin in a research communication but contained 15 additional residues.


Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2.
A single sub-anesthetic dose of ketamine produces a rapid and sustained antidepressant response, yet the molecular mechanisms responsible for this remain unclear. Here, we identified cell-type-specific transcriptional signatures associated with a sustained ketamine response in mice. Most interestingly, we identified the Kcnq2 gene as an important downstream regulator of ketamine action in glutamatergic neurons of the ventral hippocampus. We validated these findings through a series of complementary molecular, electrophysiological, cellular, pharmacological, behavioral, and functional experiments. We demonstrated that adjunctive treatment with retigabine, a KCNQ activator, augments ketamine's antidepressant-like effects in mice. Intriguingly, these effects are ketamine specific, as they do not modulate a response to classical antidepressants, such as escitalopram. These findings significantly advance our understanding of the mechanisms underlying the sustained antidepressant effects of ketamine, with important clinical implications.


S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl-2/Bcl-xL inhibition by the downregulation of survivin.
Breast cancer cells possess a deregulated apoptotic pathway with increased expression levels of anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins and ribosomal S6 kinase 1 (S6K1) protein activity. Therefore, combined interference of anti-apoptotic Bcl-2 family and S6K1 protein expression may be a reasonable therapeutic strategy for the treatment of patients with breast cancer. In the present study, it was identified that the administration of a combination of ABT263 [navitoclax; a Bcl-2/Bcl-extra large (Bcl-xL) inhibitor] and PF4708671 (an S6K1 inhibitor) markedly increased apoptotic cell death in the BT474 breast cancer cells compared with the administration of either agent alone. Furthermore, the downregulation of Bcl-2/Bcl-xL and S6K1 with small interfering RNA induced a significant increase in cell death compared with RNA interference of either agent alone. Notably, combination treatment with ABT263 and PF4708671 decreased the expression level of survivin protein, with this ectopic expression of survivin attenuating cell death. Thus, the present study determined that the combined inhibition of Bcl-2/Bcl-xL and S6K1 may be a good strategy for treating patients with breast cancer.


Identification of novel mureidomycin analogues via rational activation of a cryptic gene cluster in Streptomyces roseosporus NRRL 15998.
Antimicrobial agents are urgently needed to tackle the growing threat of antibiotic-resistant pathogens. An important source of new antimicrobials is the large repertoire of cryptic gene clusters embedded in microbial genomes. Genome mining revealed a napsamycin/mureidomycin biosynthetic gene cluster in the chromosome of Streptomyces roseosporus NRRL 15998. The cryptic gene cluster was activated by constitutive expression of a foreign activator gene ssaA from sansanmycin biosynthetic gene cluster of Streptomyces sp. strain SS. Expression of the gene cluster was verified by RT-PCR analysis of key biosynthetic genes. The activated metabolites demonstrated potent inhibitory activity against the highly refractory pathogen Pseudomonas aeruginosa, and characterization of the metabolites led to the discovery of eight acetylated mureidomycin analogues. To our surprise, constitutive expression of the native activator gene SSGG_02995, a ssaA homologue in S. roseosporus NRRL 15998, has no beneficial effect on mureidomycin stimulation. This study provides a new way to activate cryptic gene cluster for the acquisition of novel antibiotics and will accelerate the exploitation of prodigious natural products in Streptomyces.


Identification and characterization of novel alternative splice variants of human SAMD11.
Sterile alpha motif domain-containing 11 (SAMD11) is evolutionarily conserved from zebrafish to human. Mouse Samd11 is predominantly expressed in developing retinal photoreceptors and the adult pineal gland, and its transcription is directly regulated by the cone-rod homeodomain protein Crx. However, there has been little research on human SAMD11. To investigate the function of human SAMD11, we first cloned its coding sequence (CDS) and identified up to 45 novel alternative splice variants (ASVs). Mouse Samd11 ASVs were also identified by aligning the mouse Samd11 expressed sequence tags (ESTs) with the annotated sequence. However, the range of expression and transcriptional regulation of SAMD11 differs between human and mouse. Human SAMD11 was found to be widely expressed in many cell lines and ocular tissues and its transcription was not regulated by CRX, OTX2 or NR2E3 proteins. Furthermore, functional analysis indicated that human SAMD11 could promote cell proliferation slightly. In conclusion, this study elucidated the basic characteristics of human SAMD11 and revealed that, although the occurrence of alternative splicing of SAMD11 was conserved, the function of SAMD11 may vary in different species.


Per- and polyfluoroalkyl substances exposure science: current knowledge, information needs, future directions.
Per- and polyfluoroalkyl substances have been documented at all spatial scales with concerns of adverse ecological and human health effects. Human exposures and relative pathway contributions depend on the specific population, their exposure scenarios, and pathways of local sources. Provide a narrative overview of (1) current per- and polyfluoroalkyl substances knowledge for sources, concentrations, and exposures; (2) critical per- and polyfluoroalkyl substances exposure information gaps and needs, and (3) United States Environmental Protection Agency's strategies and action plans in collaboration with other federal, industrial, and academic partners. A literature review was conducted for per- and polyfluoroalkyl substances (primarily perfluorooctane sulfonate and perfluorooctanoic acid) compounds in blood, water, soil, house dust, indoor and outdoor air, consumer products, food, and fish, as well as per- and polyfluoroalkyl substances exposure modeling. Large variability exists in measured per- and polyfluoroalkyl substances environmental concentrations and human exposures. Literature indicated that ingestion of food ("background"), drinking water ("contaminated" scenarios), and house dust (for children) are main pathways for perfluorooctane sulfonate and perfluorooctanoic acid. Needs for addressing critical data gaps are identified. More information is available on long-chain per- and polyfluoroalkyl substances than for replacement and emerging compounds. A large-scale research effort by the United States Environmental Protection Agency and other federal agencies is underway for a better understanding of per- and polyfluoroalkyl substances exposures.


Non-variant specific antibody responses to the C-terminal region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1(19)) in Iranians exposed to unstable malaria transmission.
The C-terminal region of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1(19)) is a leading malaria vaccine candidate antigen. However, the existence of different variants of this antigen can limit efficacy of the vaccine development based on this protein. Therefore, in this study, the main objective was to define the frequency of PfMSP-1(19) haplotypes in malaria hypoendemic region of Iran and also to analyse cross-reactive and/or variant-specific antibody responses to four PfMSP-1(19) variant forms. The PfMSP-1(19) was genotyped in 50 infected subjects with P. falciparum collected during 2006-2008. Four GST-PfMSP-1(19) variants (E/TSR/L, E/TSG/L, E/KNG/F and Q/KNG/L) were produced in Escherichia coli and naturally occurring IgG antibody to these proteins was evaluated in malaria patients' sera (n = 50) using ELISA. To determine the cross-reactivity of antibodies against each PfMSP-1(19) variant in P. falciparum-infected human sera, an antibody depletion assay was performed in eleven corresponding patients' sera. Sequence data of the PfMSP-1(19) revealed five variant forms in which the haplotypes Q/KNG/L and Q/KNG/F were predominant types and the second most frequent haplotype was E/KNG/F. In addition, the prevalence of IgG antibodies to all four PfMSP-1(19) variant forms was equal and high (84%) among the studied patients' sera. Immunodepletion results showed that in Iranian malaria patients, Q/KNG/L variant could induce not only cross-reactive antibody responses to other PfMSP-1(19) variants, but also could induce some specific antibodies that are not able to recognize the E/TSG/L or E/TSR/L variant forms. The present findings demonstrated the presence of non-variant specific antibodies to PfMSP-1(19) in Iranian falciparum malaria patients. This data suggests that polymorphism in PfMSP-1(19) is less important and one variant of this antigen, particularly Q/KNG/L, may be sufficient to be included in PfMSP-1(19)-based vaccine.


A randomized pilot study assessing the acceptability of rapid point-of-care hepatitis C virus (HCV) testing among male inmates in Montreal, Canada.
The OraquickⓇ fingerprick point-of-care hepatitis C virus antibody (HCV-Ab) test is favoured to venipuncture among people who inject drugs; however, its acceptability in prison populations is unknown. We aimed to compare the acceptability of the OraquickⓇ versus standard venipuncture among people in prison. From October to December 2019, 280 sentenced male inmates at L'Établissement de Détention de Montréal (Quebec, Canada) were screened for participation, 150 excluded due to prior HCV screening, and 52 refused participation. The remaining 78 were randomized 1:1 to opt-out HCV-Ab screening with OraQuickⓇ or venipuncture (n = 39 each). Acceptability was determined by the proportion accepting to undergo screening. The majority of participants (median age 33 years) reported a history of drug use (76%; 8% injection drug use); 47% perceived their HCV risk to be moderate/high. All inmates randomized to OraquickⓇ accepted testing while 87% accepted venipuncture. Among those who accepted OraquickⓇ vs. venipuncture, 100% vs. 97% were satisfied with the test, 97% vs. 94% would recommend the same test, and 100% vs. 76% would choose the same test again. Adult incarcerated men in Canada were both more likely to accept OraquickⓇ compared to venipuncture, and to choose OraquickⓇ for future HCV screening.


'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.
Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.


Chemo-spectroscopic sensor for carboxyl terminus overexpressed in carcinoma cell membrane.
Certain carboxyl groups of the plasma membrane are involved in tumorgenesis processes. A gold core-hydroxyapatite shell (AuHA) nanocomposite is introduced as chemo-spectroscopic sensor to monitor these carboxyl groups of the cell membrane. Hydroxyapatite (HA) plays the role both of a chemical detector and of a biocompatible Raman marker. The principle of detection is based on chemical interaction between the hydroxyl groups of the HA and the carboxyl terminus of the proteins. The AuHA exhibits a surface enhanced Raman scattering (SERS) signal at 954 cm(-1) which can be used for its localization. The bio-sensing capacity of AuHA towards human skin epidermoid carcinoma (A431) and Chinese hamster ovary (CHO) cell lines is investigated using Raman microspectroscopic imaging. The localization of AuHA on cells is correlated with scanning electron microscopy, transmission electron microscopy and structured illumination fluorescence microscopy. This qualitative approach is a step towards a quantitative study of the proteins terminus. This method would enable further studies on the molecular profiling of the plasma membrane, in an attempt to provide accurate cell identification. Using a gold core-hydroxyapatite shell (AuHA) nanocomposite, the authors in this paper showed the feasibility of detecting and differentiating cell surface molecules by surface enhanced Raman scattering.


High levels of polymorphism found through cross-amplification of microsatellite loci in a Ctenomys pearsoni (Rodentia, Ctenomyidae) population.
Ctenomys pearsoni (Pearson's tuco-tuco) is a subterranean rodent native to Uruguay. We tested the amplification pattern of 12 microsatellite loci, designed for C. sociabilis and C. haigi in a C. pearsoni population. DNA extractions were made from hair samples, and PCR amplification products were run on an ABI 3100 microcapillary gel. Eight loci were selected to form a highly polymorphic panel that could be used to efficiently screen populations of this species. In DNA from 35 tuco-tucos, the mean polymorphic information content value was 0.6536 and the mean expected heterozygosity was 0.7166. Paternity non-exclusion probabilities for seven independent loci were NE-1P = 0.0766 and NE-2P = 0.0108, and combined non-exclusion P(ID) was 6.2 x 10(-7). This panel of microsatellite loci has sufficient power to make inferences regarding group structure, mating strategies and evolutionary relationships among populations.


Modification of serotonin neuron properties in mice lacking 5-HT1A receptors.
Using null mutant mice for the 5-HT1A receptor (5-HT1A-/-), extracellular electrophysiological recordings were first conducted to evaluate the impact of its genetic deletion on the firing rate of dorsal raphe 5-hydroxytryptamine (5-HT) neurons. Experiments were also done using brain slices to assess whether any compensation phenomenon had taken place in key receptors known to control 5-HT and norepinephrine release. The mean firing rate of 5-HT neurons was nearly doubled in 5-HT1A-/- mice, although 65% of the neurons were firing in their normal range. In preloaded brain slices, the 5-HT1D/B receptor agonist sumatriptan equally inhibited the electrically evoked release of [3H]5-HT in mesencephalic slices (containing the dorsal and median raphe) from wildtype and 5-HT1A-/- mice. The 5-HT1B receptor agonist CP 93129 (1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b) pyridin-5-one) and the alpha2-adrenoceptor agonist UK14,304 (5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) produced the same inhibitory effect in both groups of mice in hippocampus and frontal cortex slices. No difference was observed on the UK14,304-mediated inhibition of [3H]norepinephrine from preloaded slices of the two latter structures between the two groups of mice. In conclusion, the loss of control of the 5-HT1A autoreceptor in 5-HT1A-/- mice lead to a significant enhancement of 5-HT neuronal firing, but it did not alter 5-HT or norepinephrine release in any of the brain structures examined. In addition, it was not associated with changes in the function of 5-HT1D and 5-HT1B autoreceptors and of alpha2-adrenergic heteroreceptors on 5-HT neurons, nor of that of alpha2-adrenoceptors on norepinephrine terminals.


[Child health environment in the context of relocating of camp site families to social housing].
Housing interventions aimed at overcoming poverty can lead to changes in the health status of children by modifying risk factors in their physical and social environment the aim was to identify children's environmental health factors to change with the relocation of families from slums to public housing. A cross-sectional study was conducted in children ages 2-8 years old of families relocated to public housing (n=115) who were compared to children residing in slums (n=88) in Santiago, Chile. Family socioeconomic characteristics, indoor environment and neighborhoods were collected. It was included respiratory symptoms, accidents and maternal-child care of children. χ2, Fisher and Mann-Whitney test were used to compare groups. There were differences in households related to pets keeping, presence of humidity/molds in homes, types of fuels, and perceived safety problems in neighborhoods (p<0.05). The families from slums reported higher tenancy of pets (73.8% v/s 32.2%%), humidity/molds in homes (43.,2% v/s 18.3%), use of wood for heating (39.8% v/s 0.0%), compared with families of public housing. Residents of public housing perceived more safety problems in neighborhood, and children have more asthma related symptoms and have lower diversity of accidents in home. Among the factors studied, indoor air quality and safety in neighborhoods could be linked to changes from the relocation of families. This reinforces the need to deepen the positive and negative influences of residential mobility of these groups focused on child welfare perspective.


Spontaneous production of interleukin-1-like cytokine from a mouse osteoblastic cell line (MC3T3-E1).
We have investigated the role of interleukin-1 in the regulatory mechanisms of a bone remodeling system. Osteoblastic cell line (MC3T3-E1) established from newborn mouse calvaria spontaneously produced interleukin-1-like cytokine. Although the interleukin-1-like activity was not observed in culture supernatants of the cells during their exponential phase of growth, a most remarkable interleukin-1-like activity was detected in the supernatants of cells cultured in serum-free alpha-MEM on day 5 after the cells had formed a confluent monolayer. Gel filtration analysis indicated that the interleukin-1-like cytokine exhibits some heterogeneity in size.


Tardy ulnar nerve palsy in cubitus varus deformity associated with ulnar nerve dislocation in adults.
Seven patients with tardy ulnar nerve palsy from a posttraumatic cubitus varus deformity were reviewed retrospectively. The severity of symptoms was grade I in 3 patients and grade II in 4 patients according to McGowan's classification. The mean internal rotation angle was 30.7 degrees (range, 25 degrees -45 degrees ). The most prominent feature was dislocation of the nerve anterior to the medial epicondyle and entrapment of the nerve by the fibrous band of the flexor carpi ulnaris muscle. Of these 7 patients, 4 were treated by 3-dimensional osteotomy with ulnar nerve transposition, and 3 were treated by anterior transposition of the ulnar nerve. All patients improved clinically, and there was no significant difference between anterior transposition of the nerve in the group with osteotomy and the group without osteotomy. Ulnar nerve instability due to internal rotation deformity and distal entrapment was considered to be the main cause of neuropathy.


Synthesis of the tripeptide L-Trp-L-Ser-L-Glu. Comparison of its biological activity with that of the delta-sleep-inducing-peptide (DSIP).
In order to test the specificity of the natural Delta-Sleep-Inducing-Peptide (DSIP), a tripeptide with the same N-terminal amino acid was synthesized. The synthesis of the new tripeptide L-Trp-L-Ser-L-Glu was carried out by the method of the mixed anhydride. Protecting groups were all oxygen-bound benzyl groups. The physical-chemical data of the newly synthesized peptides are reported. The biological activity of the tripeptide was assayed by intraventricular infusion in the rabbit under the same conditions as for the DSIP. The effects of the tripeptide on the EEG could not duplicate those of DSIP which induced a marked increase of delta activity, typical for orthodox 'Slow Wave Sleep' (SWS).


SGLT2 inhibitors in patients with cirrhosis and diabetes mellitus: A tertiary center cohort study and insights about a potential therapeutic target for portal hypertension.
Highlights Sodium glucose cotransporter 2 (SGLT2) inhibitors have favorable pleiotropic effects in patients with diabetes mellitus and cardiovascular or renal disease. The benefits of SGLT2 inhibitors may extend to portal hypertension, but they have not been formally evaluated in patients with cirrhosis. Our study is the first to provide clinical data for SGLT2 inhibitors in a cohort of patients with cirrhosis, and our findings support ongoing evaluation in the form of a clinical trial.


[Contribution to the differential diagnosis of lung infarct, pulmonary tuberculosis and lung neoplasms].
It is reported on the rare case of a symptom-free, atypically localised haemorrhagic pulmonary infarction without provable cause in a 52-year-old male. The patient became conspicuous on account of a plum-sized focal shadow in the right lateral upper field detected during a mass examination. The state was regarded as bronchial. carcinoma. Operation and following histological investigation of the resection preparation finally resulted in the diagnosis.


Use of penile corporeal injection to assess coronal hypospadias.
Coronal hypospadias is a frequent abnormality of the genitalia. It is recommended that patients with coronal hypospadias be assessed with the technique of penile corporeal injection during anesthesia and any patient with coronal hypospadias should be circumcised with the utmost caution and surgical discretion.


Subtotal duodenectomy with jejunal patch for megaduodenum secondary to congenital duodenal malformation.
This report describes a technique devised for two children with megaduodenum consisting of subtotal duodenal resection with the proximal jejunum used as an onlay patch. A 2-year-old boy presented after unsuccessful surgical repairs for duodenal stenosis with web. Another 8-year-old boy returned from the United States after several surgical procedures for complicated congenital left diaphragmatic hernia with gastric outlet obstruction. Both boys manifested postprandial right upper abdominal fullness, occasional vomiting, abdominal pain, and failure to thrive. Upper gastrointestinal contrast study findings showed massively dilated duodenums in both patients that were larger than the stomach. During the operative procedures, about 95% of the duodenal wall was resected, leaving the basal portion that was unified with the pancreatic head and the ampulla of Vater as linguiform flap, which was covered with the proximal jejunum as an onlay patch so as to form the anterior wall of the duodenal bulb. The patients showed markedly improved quality of life and catch-up growth after the operations. The duodenal bulbs were of adequate size in follow-up gastrointestinal series. This technique will be useful in cases of functional duodenal obstruction with megaduodenum secondary to congenital duodenal malformations leading to blind loop syndrome.


CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of feline immunodeficiency virus infection.
Acute lentiviral infection is characterized by early CD8(+) cytotoxic T cell (CTL) activity and a subsequent decline in plasma viremia. However, CD8(+) lymphocytes fail to eliminate the virus and a progressive T cell immune dysfunction develops during the course of chronic lentiviral infection. To further define this CD8(+) immune dysfunction we utilized PARR (PCR for antigen receptor rearrangements), a technique which measures clonally expanded lymphocyte populations by comparison of highly conserved T cell receptor (TCR) regions to identify the prevalence of clonal CD8(+) T cells following FIV infection. We then compared phenotype, mRNA profiles, CD8(+) proliferation and plasma viremia during acute and chronic infection for PARR positive (PARR(+)) and PARR negative (PARR(-)) Feline Immunodeficiency Virus (FIV) infected cats. We demonstrated that approximately forty percent of the FIV(+) cats examined exhibit CD8(+) clonality compared to none of the FIV(-) control cats. There were no phenotypic differences between PARR(+) and PARR(-) CD8(+) lymphocytes from FIV(+) cats but retrospective analysis of plasma viremia over the course of infection revealed a delayed peak in plasma viremia and a decline in lymphocyte counts were observed in the PARR(+) group during acute infection. CD8(+) lymphocytes isolated from chronically infected PARR(-) cats exhibited significantly higher mRNA expression of IFN-γ and IL-2 following mitogenic stimulation when compared to PARR(+) CD8(+) lymphocytes. These data suggest that clonal CD8(+) expansion may be related to impaired control of acute viremia and less effective CD8(+) anti-viral function. Using PARR to assess changes in CD8(+) clonality during the progression from acute to chronic FIV infection may help to better characterize the factors which contribute to CD8(+) anergy and lentiviral persistence.


Fixation Versus Replacement in Geriatric Hip Fractures: Does Functional Outcome and Independence in Self-Care Differ?
Although there is evidence of improved functional outcomes with our "integrated care pathway" for geriatric hip fractures, we do not know if there is a significant difference in functional recovery of activities of daily living and attainment of independence in self-care between patients who underwent fixation and those treated with arthroplasty. To determine whether such a difference exists in surgically fixed hip fractures. Patients with hip fracture treated surgically were divided into group A (internal fixation, n = 213) and group B (arthroplasty, n = 199). Demographic data, Charlson comorbidity index (CCI) score, time to surgery, and length of stay were recorded. Inpatient complications and mortality rates were also documented. Modified Barthel Index (MBI) scores were recorded for the following intervals: prefall, discharge, 6-month, and at 1-year follow-up. The mean age (A: 80 years and B: 81years), CCI (A: 5.41 and B: 5.43), and length of stay (A: 13.6 days and B: 15.2 days) were not significantly different. However, there was a significant difference (P < .05) in time to surgery (A: 102.2 hours and B: 86.6 hours). Complication rates were about 6% in both groups (A = 6.57%: urinary infections = 13, wound infections = 1 and B = 6.03%: urinary infections = 10, wound infections = 1, pressure ulcer = 1). The preinjury MBI scores were significantly different (P < .05; A: 91.65 and B: 88.19), however, there was no significant difference in scores measured at discharge (A: 60.79 and B: 59.39), 6 months (A: 77.65 and B: 77.47) and 1 year (A: 80.71 and B: 83.03). Patients who underwent surgery for hip fracture had overall recovered 90.9% of their preinjury function (overall MBI at 1 year: 81.83). The MBI scores reflect the extent of attainment of independence in self-care, and actual functional recovery is gauged from the percentage of recovery of preinjury function at 1 year postsurgery. We conclude that the type of surgery may not be a significant factor in determining independence in self-care although patients who had arthroplasty had recovered more function at 1 year postsurgery than those who underwent fixation (percentage recovery of preinjury function-A: 88.1% and B: 94.1%).


Mitochondrial NO and reactive nitrogen species production: does mtNOS exist?
It is more than 10 years now that mitochondria are suspected to be sources of nitric oxide (NO). This hypothesis is intriguing since NO has multiple targets within the organelle and it is even suggested that mitochondria are the primary targets of NO in the cell. Most remarkably, nanomolar concentrations of NO can inhibit mitochondrial respiration, so even a small amount of NO in the mitochondrial matrix may regulate ATP synthesis. Therefore, the idea that mitochondria themselves are capable of NO production is an important concept in several physiological and pathological mechanisms. However, this field of research generates surprisingly few original papers and the published studies contain conflicting results. The reliability of the results is frequently questioned since they are seldom reproduced by independent investigators. Until 2003, all papers published in this field showed affirmative results but since then several studies directly challenged the existence of a mitochondrial nitric oxide synthase. The present review aims to summarize the most recent developments in mitochondrial NO production, highlights a few unsolved questions, and proposes new directions for future work in this research area.


Estimating the quality of eukaryotic genomes recovered from metagenomic analysis with EukCC.
Microbial eukaryotes constitute a significant fraction of biodiversity and have recently gained more attention, but the recovery of high-quality metagenomic assembled eukaryotic genomes is limited by the current availability of tools. To help address this, we have developed EukCC, a tool for estimating the quality of eukaryotic genomes based on the automated dynamic selection of single copy marker gene sets. We demonstrate that our method outperforms current genome quality estimators, particularly for estimating contamination, and have applied EukCC to datasets derived from two different environments to enable the identification of novel eukaryote genomes, including one from the human skin.


Evaluation of behavior, growth, and swarming formation of Escherichia coli and Staphylococcus aureus in culture medium modified with silver nanoparticles.
Silver nanoparticles (AgNPs), as well as silver ions, are described as toxic to a broad spectrum of microorganisms, especially bacteria. In contrast to this, a current trend is to develop and carry out the in vitro cultivation of microorganisms, facilitating the study of interactions between populations of cells and species. Thus, the goal of this study was to evaluate the behavior, growth, and swarming formation of bacteria under conditions of co-culture in solid medium modified with AgNPs. The aqueous extract from the leaves of Handroanthus serratifolius was used to chemically reduce silver nitrate (AgNO3) solution, forming AgNPs. This synthesis route was performed in an aqueous medium at 50 °C for 3 h. The hydrodynamic diameter (HD) and polydispersity index (PdI) were obtained by dynamic light scattering (DLS), and Zeta potential (ZP) of the AgNPs were measured by electrophoretic mobility. Atomic force microscopy (AFM) was used to evaluate the shape of the AgNPs. Luria Bertani (LB) medium was used for the liquid culture steps and for the solid medium, bacterial agar was added. Solutions containing AgNPs or AgNO3 were added at final concentrations of 256, 128, or 64 μM. Subsequently, microorganism Escherichia coli ATCC® 8739 and Staphylococcus aureus ATCC® 25923 were plated with AgNPs, AgNO3, and control media. Analyses of the AgNPs showed an average HD of 76.02 ± 3.08 nm, PdI of 0.461 ± 0.012, and ZP of -21.5 ± 2.2 mV; in addition, AgNPs were nearly spherical. The solid culture medium elaborated and modified with AgNPs at the concentrations of 256 and 128 μM inhibited the growth of the tested microorganisms and decreased the swarming formation. However, those media modified at a concentration of 64 μM did not induce any alteration in the growth and proliferation of the microorganisms. Furthermore, it was observed that plates containing modified culture media with 128 μM, increased proximity between both co-cultured bacteria occurred. Thus, the application of AgNPs in solid culture media becomes a promising and potentially reproducible strategy for evaluating the behavior, swarming formation, and toxicity of AgNPs, making the understanding of possible bactericidal or bacteriostatic effects, and also colonizing strategies.


Organogenic events during gynoecium and fruit development in Arabidopsis.
Angiosperms are the most successful group of land plants. This success is mainly due to the gynoecium, the innermost whorl of the flower. In Arabidopsis, the gynoecium is a syncarpic structure formed by two congenitally fused carpels. At the fusion edges of the carpels, the carpel margin meristem forms. This quasi-meristem is important for medial-tissue development, including the ovules. After the double fertilization, both the seeds and fruit begin to develop. Due to the importance of seeds and fruits as major food sources worldwide, it has been an important task for the scientific community to study gynoecium development. In this review, we present the most recent advances in Arabidopsis gynoecium patterning, as well as some questions that remain unanswered.


[Surgical strategy for neck burns and their sequelae].
Burns of the neck are common and expose them to functional and aesthetic complications which are sometimes very serious. Care in the acute stage and treatment of sequelae contribute to a common goal of restoration: Maintain or recreate a chin-neck angle and get a quality skin as close as possible to the original skin, in terms of flexibility, texture, thickness and color. The wide variety of cases encountered requires knowing the armamentarium available to us today, and the anatomical basis and clinical underlying indications.


Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation.
Cap-dependent binding of mRNA to the 40 S ribosomal subunit during translational initiation requires the association of eukaryotic initiation factor 4G (eIF4G; formerly eIF-4 gamma and p220) with other initiation factors, notably eIF4E, eIF4A, and eIF3. Infection of cells by picornaviruses results in proteolytic cleavage of eIF4G and generation of a cap-independent translational state. Rhinovirus 2A protease and foot-and-mouth-disease virus L protease were used to analyze the association of eIF4G with eIF4A, eIF4E, and eIF3. Both proteases bisect eIF4G into N- and C-terminal fragments termed cpN and cpC. cpN was shown to contain the eIF4E-binding site, as judged by retention on m7GTP-Sepharose, whereas cpC was bound to eIF3 and eIF4A, based on ultracentrifugal co-sedimentation. Further proteolysis of cpN by L protease produced an 18-kDa polypeptide termed cpN2 which retained eIF4E binding activity and corresponded to amino acid residues 319-479 of rabbit eIF4G. Further proteolysis of cpC yielded several smaller fragments. cpC2 (approximately 887-1402) contained the eIF4A binding site, whereas cpC3 (approximately 480-886) contained the eIF3 binding site. These results suggest that cleavage by picornaviral proteases at residues 479-486 separates eIF4G into two domains, one required for recruiting capped mRNAs and one for attaching mRNA to the ribosome and directing helicase activity. Only the latter would appear to be necessary for internal initiation of picornaviral RNAs.


Cerium dioxide nanoparticles modulate antioxidant defences and change vascular response in the human saphenous vein.
Nanoparticles have a promising future in biomedical applications and knowing whether they affect ex vivo vascular reactivity is a necessary step before their use in patients. In this study, we have evaluated the vascular effect of cerium dioxide nanoparticles (CeO2NPs) on the human saphenous vein in response to relaxing and contractile agonists. In addition, we have measured the protein expression of key enzymes related to vascular homeostasis and oxidative stress. We found that CeO2NPs increased expression of both SOD isoforms, and the consequent reduction of superoxide anion would enhance the bioavailability of NO explaining the increased vascular sensitivity to sodium nitroprusside in the presence of CeO2NPs. The NOX4 reduction induced by CeO2NPs may lead to lower H2O2 synthesis associated with vasodilation through potassium channels explaining the lower vasodilation to bradykinin. In addition, we showed for the first time, that CeO2NPs increase the expression of ACE2 in human saphenous vein, and it may be the cause of the reduced contraction to angiotensin II. Moreover, we ruled out that CeO2NPs have effect on the protein expression of eNOS, sGC, BKca channels and angiotensin II receptors or modify the vascular response to noradrenaline, endothelin-1 and TXA2 analogue. In conclusion, CeO2NPs show antioxidant properties, and together with their vascular effect, they could be postulated as adjuvants for the treatment of cardiovascular diseases.


Antibiotic Resistance Profile of Common Bacteria Isolated from Blood Stream, Lower Respiratory Tract and Urinary Infections in Intensive Care Unit in Saudi Arabia: A Retrospective Study.
The rate of infections in the intensive care units (ICUs) is rising, mainly because of the increasing use of invasive procedures and specialized devices. This study aimed to identify the antibiotic resistance profile of common bacteria isolated from lower respiratory tract infections (LRTIs), bloodstream infections (BSIs), and urinary infections (UTIs) in ICUs in Saudi Arabia. In the current retrospective study, the isolates and antibiotic resistance were collected from the Electronic Medical Record (EMR) for respiratory, blood, and urine samples. The study sample compromised 96 patients admitted to the ICU at least for 48 hours and have a central venous catheter (CVC) between November 1, 2020, and January 31, 2021. 66 (68.8%) of the study sample were males, and 30 (31.2%) were females. LRTIs were the most common isolates (51 samples), followed by BSIs (28 samples) and UTIs (17 samples). The isolated pathogens in this study were Klebsiella pneumoniae (K. pneumoniae) (59.4%), Coagulase-negative staphylococci (CoNS) (11.5%), Escherichia coli (E. coli) (8.4%), Acinetobacter baumannii (A. baumannii) (7.3%), and Staphylococcus aureus (S. aureus) (6.2%). BSI were frequently caused by CoNS (35.7%) and K. pneumoniae (35.7%), while Methicillin-resistant Staphylococcus aureus (MRSA) represented 10.7% of BSI. Vancomycin, Synercid, and Teicoplanin were the commonly used antibiotics and showed 100% sensitivity among S. aureus, including MRSA, while almost 100% resistance was observed for penicillin and oxacillin against the same organisms. The maximum resistance was observed with aztreonam (96.4%), ampicillin (87.3%), followed by co-amoxiclav (83.9%), cotrimoxazole (79.5%) and cephalosporin group antibiotics. Strict adherence to infection prevention practices and wise use of antibiotics are recommended to slow the spread of antimicrobial resistance (AMR).


Total immunoreactive angiotensin ii, its hepta-octapeptide fraction, and its hexapeptide in patients with liver disease.
Arterial and venous plasma concentrations of total immunoreactive angiotensin II (AT II), its bioactive hepta-octapeptide fraction and its inactive hexapeptide were measured in normal subjects (n=16), in patients with acute viral hepatitis (n=12), and in treated (n=16) and untreated (n=17) patients with cirrhosis of the liver and ascites. Independent of normal or increased values of total immunoreactive AT II, the ratio between the hepta-octapeptides and the hexapeptide remained unchanged. This might indicate continuous octapeptide generation and balanced metabolite turnover throughout the systemic circulation. Moreover, a significant arterio-venous peptide gradient was lacking. It has to be concluded that total venous plasma AT II sufficiently reflects both the arterial hormone concentration and its major fraction of hepta-octapeptides in arterial (79%) and venous (76%) blood.


Genetic variants of tumor necrosis factor-α -308G/A (rs1800629) but not Toll-interacting proteins or vitamin D receptor genes enhances susceptibility and severity of malaria infection.
Susceptibility to malaria infection has been associated with host genetic polymorphisms that differs between groups. We hypothesize that Toll-interacting proteins (TOLLIP), vitamin D receptor (VDR) and tumor necrosis factor-α (TNF) genes are significant contributors to susceptibility and disease severity in Plasmodium falciparum (Pf) infection. Our aim is to explore the genomic diversity and haplotype frequency of these genes, as well as extrapolate possible association with markers of severity, between malaria-infected and healthy controls. Genomic DNA samples extracted from the blood of 107 malaria-infected patients and 190 uninfected controls were analyzed, with no difference in genotypic or allelic frequencies of TOLLIP and VDR polymorphisms. However, a significant difference in the genotypic (p = 2.20E-16) and allelic frequencies (p = 2.20E-16) of the TNF-α (snp rs1800629) polymorphism was found. The preponderance of the mutant variant among the malaria-infected show a possible impaired capacity to mount an effective immune response, potentially confirmed by our association results. This result calls for analysis of clearly delineated uncomplicated versus severe disease groups, including serum assays, providing a basis to conclude that susceptibility to malaria infection and potential contribution to disease severity is significantly associated with polymorphisms of the tumor necrosis factor-α but not TOLLIP or VDR genes.


Comment on "An alternative Avrami equation to evaluate kinetic parameters of the interaction of Hg(II) with thin chitosan membranes," by E.C.N. Lopes, F.S.C. dos Anjos, E.F.S. Vieira, and A.R. Cestari.
A history of using and applying Ho's pseudo-second-order kinetic expression for adsorption systems is presented. A reference section in a paper is important to researchers interested in the paper's statement and in following the study or finding useful information from the paper. This section is as important as the core of a paper. This comment offers information on citing the original idea of pseudo-second-order kinetic expression.


Preventive effect of aripiprazole once monthly on rehospitalization for bipolar disorder: A multicenter 1-year retrospective mirror image study.
We conducted a 1-year retrospective mirror-image study to investigate the effect of aripiprazole once monthly (AOM) on rehospitalization for bipolar disorder. Participants were recruited from psychiatric emergency and acute care hospitals in western Japan. We included 39 participants with bipolar disorder who had been administered AOM for at least 1 year with no missing medical records during the observational period. The primary outcomes were rehospitalization rate, number of rehospitalizations, total hospitalization days, and time to rehospitalization in the context of overall psychiatric readmissions. The significance level was set at p < 0.05. AOM significantly reduced the rehospitalization rate from 23/39 (59%) to 7/39 (18%) (p = 0.001). The number of rehospitalizations decreased significantly from a mean of 0.85 per person-year to 0.41 per person-year (p = 0.048). The total hospitalization days significantly decreased from a mean of 34.9 days to 14.4 days (p = 0.008). AOM significantly prolonged the time to rehospitalization (p < 0.001). This study found that AOM reduces overall psychiatric rehospitalization for bipolar disorder based on data from 1 year before and after AOM administration in the real-world setting. Future studies should examine the robustness and persistence of the rehospitalization preventive effect of AOM with larger sample sizes and longer observation periods beyond 1 year.


Extinction and climate change.
Arising from F. He & S. P. Hubbell 473, 368-371 (2011). Statistical relationships between habitat area and the number of species observed (species-area relationships, SARs) are sometimes used to assess extinction risks following habitat destruction or loss of climatic suitability. He and Hubbell argue that the numbers of species confined to-rather than observed in-different areas (endemics-area relationships, EARs) should be used instead of SARs, and that SAR-based extinction estimates in the literature are too high. We suggest that He and Hubbell's SAR estimates are biased, that the empirical data they use are not appropriate to calculate extinction risks, and that their statements about extinction risks from climate change do not take into account non-SAR-based estimates or recent observations. Species have already responded to climate change in a manner consistent with high future extinction risks.


siRNA and miRNA processing: new functions for Cajal bodies.
In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) regulate important processes that include mRNA inactivation, viral defense, chromatin modification, and transposon silencing. Recently, nucleolus-associated Cajal bodies in plants have been implicated as sites of siRNA and miRNA biogenesis, whereas in animals siRNA and miRNA dicing occurs in the cytoplasm. The plant nucleolus also contains proteins of the nonsense-mediated mRNA decay pathway that in animals are found associated with cytoplasmic processing bodies (P-bodies). P-bodies also function in the degradation of mRNAs subjected to miRNA and siRNA targeting. Collectively, these observations suggest interesting variations in the way siRNAs and miRNAs can accomplish their similar functions in plants and animals.


Translocation of arsenic contents in vegetables from growing media of contaminated areas.
The aim of this study was to evaluate the translocation of arsenic (As) by different vegetables grown in agricultural soil irrigated for long period with tube well water as test vegetable samples and compared those vegetables of same species grown in agricultural soil irrigated with fresh canal water marked as control vegetable samples. Moreover, the total and ethylene-diamine-tetra acetic acid (EDTA) extractable contents of As in soil irrigated by tube well and canal water were determined and correlate with total concentrations of As in edible parts of vegetables. Statistically significant correlations were obtained between the total and EDTA extractable fractions of As in soil. High level of total and EDTA extractable As were found in tested vegetable samples as compared to controlled vegetable samples. This investigation highlights the increased danger of growing vegetables in the agricultural land continuously irrigated by As contaminated water.


Site discrimination in the crystalline borophosphate Na5B2P3O13 using advanced solid-state NMR techniques.
A comprehensive solid-state NMR investigation on crystalline Na(5)B(2)P(3)O(13) is presented. Triple-quantum magic angle spinning (TQMAS) and rotational echo double resonance (REDOR) studies are used for accurate determinations of the (11)B, (23)Na and (31)P interaction parameters. Based on these results and complementary quantum mechanical calculations, plausible site assignments can be derived. Generally, the results show that detailed, quantitative information about structures in borophosphate compounds can be obtained by investigating both the local site environments characterized by chemical shift and quadrupolar interaction parameters and the correlated dipolar interactions to atoms in the second coordination sphere.


Xihuang pill ameliorates colitis in mice by improving mucosal barrier injury and inhibiting inflammatory cell filtration through network regulation.
The prevalence of colitis is on the rise, and effective treatment options are currently lacking. Xihuang pill (XHP) is a traditional Chinese medicine formula mentioned in the "Volume 4 of Surgical Evidence and Treatment of the Whole Life" authored by the renowned doctor Hong-Xu Wang during the Qing Dynasty. It is now part of the "Volume 9 of Chinese medicine formula preparation in Drug Standard." XHP and its primary ingredients have been demonstrated anti-inflammatory properties against colitis. However, the specific effects and underlying mechanisms of XHP in treating colitis remain unknown. This study aimed to investigate the potential impact of XHP on colitis and uncover the underlying mechanisms involved. An acute colitis model was developed in C57BL/6N mice, and the effects on weight loss, colon length, the permeability of the colonic mucosa barrier, Claudin-5 and Occludin expression, number of both infiltrating MPO-positive cells and CD68-positive cells, and the content of pro-inflammatory cytokines (IL-6, IL-22, IL-1β, and TNF-α) in the colon tissue were investigated. Low-, medium-, and high-dose XHP (0.45, 0.9, and 1.8 g/kg/day) (batch number: z21021222) were administered to the mice by gavage over the course of two weeks. Additionally, the protein expression levels in colon tissue from the control group, colitis group, and XHP low-dose administration group mice were analyzed by quantitative proteomics techniques. The comprehensive profiling and characterization of absorbed components in mice blood following oral administration of XHP were identified by HPLC/Q-TOF-MS techniques, and the absorbed components in blood were combined with proteomics to reveal the mechanism of enteritis inhibition by XHP. Our findings indicated that XHP enhanced weight loss and colonic shortening of colitis mice. Additionally, XHP reduced the increase in permeability of the colonic mucosa barrier and decreased expression of Claudin-5 and Occludin, while significantly reducing the number of infiltrating MPO-positive cells and CD68-positive cells in the colon tissue. We found that XHP reduced the production of pro-inflammatory cytokines, including IL-6, IL-22, IL-1β, and TNF-α in colon tissue. Pharmacokinetic analysis suggested that XHP contained 24 blood-entering prototype ingredients, which improved colitis through the regulation of various proteins (e.g., Ctsb, Sting1, and Abat) linked to mucosal barrier injury and inflammation. XHP improved intestinal mucosal barrier injury and reduced MPO-positive cells and CD68-positive cell infiltration through multiple targets and pathways, providing support for XHP as a promising therapy for colitis.


Determination of verapamil and norverapamil in human biological material. Investigation of plasma concentrations after oral administration of two different verapamil formulations.
A method for the simultaneous determination of the cardiovascular agent verapamil and its major metabolite norverapamil in human plasma is described. Analysis is performed after alkaline extraction with n-heptane by subsequent ion-paired high performance liquid chromatographic (HPLC) separation, and direct fluorimetric measurement of both compounds (lambda maxex. = 278 nm, lambda maxem. = 320 nm). The sensitivity of the procedure (detection limit less than 1 ng/ml) is suitable for pharmacokinetic studies after therapeutic doses. The applicability of the method was tested by performing a clinical study. Plasma concentrations of two verapamil formulations for oral administration were examined. The active metabolite norverapamil was included in the investigation.


Relationship between infant death and maternal age. Comparison of sudden infant death incidence with other causes of infant mortality.
The high incidence of sudden infant death syndrome in infants born to teenage mothers prompted us to search for epidemiologic clues that might relate to SIDS causation. The death rate for SIDS was compared with that of other major causes of infant mortality in two maternal age groups (younger than 20 years and 30 to 34 years). In the neonatal period, a significantly greater overall mortality occurred in infants born to the younger mothers. This difference was primarily related to an excess of low-birth-weight infants dying from diseases of early infancy. "Weight-specific" mortality, however, was similar for the two groups. In the postneonatal period, when most SIDS occurs, the incidence was 5.2 per 1000 among infants of teenage mothers, compared with 1.0 in infants of the older mothers. A similar maternal-age-related incidence was observed for death from infections, accidents, and "other causes." By contrast, death from congenital anomalies was unrelated to maternal age in both periods. We conclude that many postneonatal deaths are influenced by environmental factors, including the age and maturity of the mother.


Impact of microfiber pollution on aquatic biota: A critical analysis of effects and preventive measures.
The widespread use of Personal protective equipments (PPEs) by the healthcare professionals and public due to Corona Virus Disease (COVID-19) pandemic has become a new source for MFs pollution. Mismanaged plastic wastes and random dispose of used surgical face mask end up in large aquatic bodies via small waterways and waste water treatment plants (WWTPs). Microplastics/Microfibres (MPs/MFs) have recently been reported in a variety of aquatic and terrestrial ecosystems, including water, deep sea sediments, air and soil. Natural components like UV radiation and temperature play a major role in weathering of surgical masks. High loads of MPs/MFs emitted into the aquatic environment are easily consumed by organism's habitat in such ecosystem by disrupting the food chain and causing chronic health problems in the organisms including humans. The aim of this review article is to shed light on these issues and compile the most recent information available regarding the deterioration of surgical face masks in the environment as well as other contaminants and their presence in various environments, particularly with regard to methods that make use of exposure models, biomarkers of exposure, and their limitations. Along with this, the study focuses on identifying gaps in current understanding and highlighting prospective research directions. The literature on surgical face mask pollution and its effects on the biological and physiological systems of various organisms and ecosystems is critically analysed in this review. It also raises awareness of how to properly dispose of used surgical face masks and other PPEs.


Comparison of fast Fourier transform and autoregressive spectral analysis for the study of heart rate variability in diabetic patients.
Impaired heart rate variability (HRV) is associated with poor outcome in diabetic patients. The present prospective study compared spectral components of HRV obtained by either fast Fourier transform (FFT) or autoregressive (AR) analyses in diabetic patients. Thirty patients (49+/-12 years; 11 F/19 M; 60% with insulin-dependent type 1 diabetes) underwent 24-h ambulatory electrocardiographic recordings which comprised a 10-min resting period at the onset (n=30) and end (n=12) of the monitoring. Spectral analysis was applied to 5-min sequences at rest, and the total power and power spectra integrated over the very low (VLF), low (LF), and high (HF) frequency bands were obtained. Fifteen patients had moderately depressed HRV and two patients had highly depressed HRV (standard deviation of the RR intervals over 24-h<100 ms and <50 ms, respectively). Both raw data and ln-transformed data were significantly different between FFT and AR. All spectra component were obtained in each patient using FFT. Using AR, the LF/HF ratio could not be estimated or was zero in 4 and 11 patients, respectively. The AR results were more sensitive than FFT results to minor changes (+/-5%) in the timing of the onset of analysis. The day-to-day reproducibility of FFT was better than that of AR. Finally, using FFT, the LF/HF ratio, LFnu, and HFnu were essentially redundant (nu=normalized units). The spectral components of short-term HRV calculated by using the FFT and AR methods were not interchangeable and FFT analysis must be preferred in diabetic patients.


Maintenance and Welfare of Parents and Senior Citizens Act 2007: A Critical Appraisal.
The sociocultural changes associated with globalization and development have weakened the traditional values and family support systems for senior citizens (age 60 years and above). There is an increase in the prevalence of elder abuse and difficulties in getting appropriate care and support. This has mandated legal measures to protect the rights of the senior citizens and provide them care and support by the family and other stakeholders. Consequent to being the signatory for the "Madrid International Plan of Action on Ageing, 2002," several countries, including India, have introduced legislation for the social protection of senior citizens. "The Maintenance and Welfare of Parents and Senior Citizens(MWP) Act, 2007" is an important legislation in India to safeguard the elderly from exploitation and abuse. This article critically evaluates the implementation of the MWP Act, 2007, and the related challenges in protecting senior citizens from abuse. The article will also highlight the proposed amendments in the Act to strengthen the effective implementation of legal protection for senior citizens and ensure their well-being and dignity. The MWP act is an important legal measure to ensure mainatinence and welfare of senior citizens and protect them from abuse and neglect. There is an immediate need to incorporate the necessary amendments so that the act gets more pragmatic value and becomes and important tool for elderly care and protection and reduce vulnerabilities and ensure holistic care with support in various bio-psycho-social domains.


Cavernous sinus air in a patient with basilar skull fracture: CT identification.
Air within the cavernous sinus resulting from fracture of the wall of the sphenoid sinus was identified by cranial CT in a patient with head injury. Careful search of the skull base is important in post-traumatic pneumocephalus to identify a potential site of CSF leak.


Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate.
Early initiation of effective treatment favours remission in rheumatoid arthritis, but it remains unknown if the same concept applies to psoriatic arthritis (PsA). Therefore, this study investigated whether the combination of golimumab plus methotrexate (MTX) as a first-line treatment is superior to MTX alone in inducing remission in PsA. This investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial included 51 MTX and bDMARD-naive patients with PsA fulfilling the CASPAR criteria and with active disease at baseline (≥3 swollen joint count/tender joint count). Patients were randomised to golimumab (50 mg SC monthly)+MTX (n=26) (TNFi arm) or matched placebo+MTX (n=25) (MTX arm). MTX was started 15 mg/week and increased to 25 mg/week over 8 weeks. The primary endpoint was percentage of patients achieving Disease Activity Score (DAS) remission (<1.6) at week 22. Safety was assessed throughout the study. The primary efficacy endpoint was achieved by 81% in the TNFi arm versus 42 % in the MTX arm (p=0.004). This difference in DAS remission was already observed at week 8. A significant difference in favour of the golimumab+MTX arm at week 22 was also observed for other response criteria such as MDA, ACR20/50/70, disease measures and patient-reported outcomes. The occurrence rates of adverse event and treatment-emergent adverse event were similar in both arms. In patients with early PsA, DAS remission at week 22 was almost doubled with golimumab+MTX versus MTX alone. This double-blind, randomised, placebo-controlled study supports the concept that early initiation of TNFi in patients with PsA favours remission. NCT01871649.


[Production of histamine induced by a lymphokine during infection with Nippostrongylus brasiliensis].
Spleen cells from Mice infected with N. brasiliensis produce a large amount of histamine in response to adult worm antigenic extract, to con A, or during primary MLC. During worm antigenic or con A response, this phenomenon results from an increase in HCSF production and HCSF sensitivity. During primary MLC, only an increase in HCSF sensitivity is observed without increase in HCSF production. This increase in histamine and HCSF production is correlated with the "self-cure" phenomenon.


Associations between recalled use of legal UK youth gambling products and adult disordered gambling.
The UK allows a number of gambling products to be legally used by people under the age of 18. The aim of this study was to explore associations between recalled legal usage of five youth gambling products and adult disordered gambling. A retrospective cross-sectional study of 1,057 adult UK gamblers, aged 18-40. Recalled legal use of five youth gambling products (category D fruit machines, coin push machines, crane grab machines, the National Lottery, and National Lottery scratchcards) was correlated with adult disordered gambling symptoms as measured by the Problem Gambling Severity Index (PGSI). Recalled rates of legal engagement with each product ranged from 50.9% for Category D fruit machines to 96.6% for coin push machines. For category D fruit machines, the National Lottery, and National Lottery scratchcards, merely having legally engaged with these products as a child was associated with adult disordered gambling. Furthermore, higher levels of recalled legal youth usage with each of the five products was also associated with adult disordered gambling. These results relate to recent government proposals to increase the National Lottery scratchcard legal age to 18, and add to a wider literature on youth gambling and subsequent gambling-related harm.


Retrospective study of radiotherapy for lung cancer in patients aged 75 years and over.
Radiotherapy is widely used in the management of lung cancer but there are few data on its use in elderly patients. Retrospective review of case notes of all patients aged 75 years and over referred to a regional centre for radiotherapy with a diagnosis of lung cancer over 1 year. Of 149 patients referred, full information was available on 144 (97%); age range 75-93 years (mean 79). Main referral sources were chest physicians [68 (44%)], general physicians [40 (28%)] and geriatricians [20 (14%)]; all patients were accepted for radiotherapy. One hundred and thirty-four (93%) had palliative treatment with most [129 (90%)] receiving 1-5 fractions over 1 week and 117 (81%) having treatment as an outpatient. Palliation appeared good for haemoptysis but less effective for the more common symptoms of dyspnoea and cough. Side effects were reported by 25 patients (18%) and were usually mild. Radiotherapy for lung cancer in this selected group of elderly patients is well tolerated with responses similar to those in younger patients.


Regulation of calcitonin and parathyroid hormone secretion by oestrogens.
Calcitonin is a peptide hormone secreted by C-cells which, in humans, are found mainly in the thyroid gland. It now seems that a major physiological function of this hormone in man is the long-term maintenance of the skeleton achieved by control of bone resorption. A marked sex difference in circulating calcitonin levels normally exists, with a relative deficiency in women as compared to men. It has now been found that oestrogens regulate calcitonin secretion and it appears likely that the loss of ovarian function at the menopause accelerates the natural decline in calcitonin secretion which occurs with age. Thus, post-menopausal women are more markedly calcitonin-deficient. Levels of the bone-resorbing hormones, parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D are not elevated post-menopausally and it seems likely that the increased bone resorption which leads to post-menopausal bone loss is due mainly to the loss of oestrogen and calcitonin secretion.


Oxotremorine- and atropine-induced changes of dopamine metabolism in the rat striatum.
The effects of various doses of oxotremorine and of atropine (30 min, i.p.) on the metabolism of dopamine were examined in the striatum of the rat. Changes in striatal dopamine metabolism were estimated by following either the accumulation of [3H] dopamine 15 min after intravenous injection of [3H] tyrosine or the accumulation of dopa (taken as an index of dopamine synthesis) in animals pretreated with a dopa decarboxylase inhibitor Ro4-4602. Oxotremorine, 0-1 mg kg-1, and atropine, 1 mg kg-1, did not affect dopamine metabolism. Oxotremorine, 0-5 and 1-5 mg kg-1, did not modify dopamine concentrations but increased the accumulation of [3H]dopamine. The drug enhanced dopa formation in animals pretreated with Ro4-4602. Atropine, 5 and 20 mg kg-1, increased the accumulation of [3H]dopamine but did not affect dopamine concentrations. The accumulation of dopa was not modified there being no difference from the saline value in animals pretreated with the dopa decarboxylase inhibitor at high dopamine metabolism and atropine reduced dopamine utilization.


An 8-year retrospective review of emergency laparotomy outcomes in a Queensland rural hospital.
Emergency laparotomy (EL) is a major operation performed in critically unwell patients. The National Emergency Laparotomy Audit (NELA), undertaken in the UK since 2013 has shown progressive improvement in clinical outcomes, specifically reduced mortality, and length of stay (LOS) through the implementation of perioperative key performance indicators (KPIs) (ANZ J Surg. 2021;91:2575, Br J Surg. 2015;102:57, Br J Surg. 2017;104:463, JAMA Surg. 2019;154:e190145). The objective is to generate a rural hospital EL audit (MELA) to evaluate local outcomes and clinical standards of practice with regional, national, and international benchmarks. A review of medical records between January 2014 and December 2021 of patients who undergo an EL. Data collected include patient demographics, clinical information, compliance to KPIs and the primary outcomes of 30-day mortality and LOS. This is a descriptive quantitative study. The inclusion and exclusion criteria were similar to those defined in NELA and ANZELA-QI. The general surgeons at the rural hospital provide emergency surgery services for the North-West Queensland community. To review local clinical outcomes of 30-day mortality, LOS, and adherence to perioperative KPIs. Overall, 84 patients met inclusion criteria. The median age (IQR) was 61 (48.8-70.3) years. The 30-day mortality was 3.6% and mean LOS was 12.8 (±13.4) days which was secondary to the low-risk patients within the data set. Compliance to KPIs (≥80%) was achieved in five of eight standards assessed. Local outcomes appear to be comparable to national and international benchmarks and a similar rural setting. The audited cohort outperformed the national standard in adherence to perioperative KPIs.


Factors affecting the reassociation and reactivation of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.
The pigeon liver fatty acid synthetase complex (14 S) is dissociated in low ionic strength buffer containing dithiothreitol to form a half-molecular weight subunits (9 S) which are completely inactive for the synthesis of saturated fatty acids. The dithiothreitol-protected (reduced) subunits are rapidly reassociated and reactivated to form the active enzyme complex, not only by an increase in salt concentration but also by micromolar concentrations of NADP+ or NADPH. Increases in KCl or NADPH concentration result in an increase in the extent of reactivation (equilibrium) with no change in the over-all rate of the reaction or the half-life ofreactivation of the enzyme. The extent (equilibrium) of reactivation of the enzyme is the same in 0.2 M potassium phosphate buffer, pH 7.0; 0.2 M KCl in 5 mM Tris-35 mM glycine buffer, PH 8.3; and 50 muM NADP+ or NADPH in the Tris-glycine buffer. The extent and rate of reactivation of the enzyme is dependent not only on ionic strength and NADPH concentration, but also on pH and temperature. Reactivation with 0.2 M KCl is optimal between pH 7.3 and 8.5. At higher and lower pH values the rate and extent of reactivation are lowered. The rate and extent of reactivation are also decreased as the temperature is lowered below 10 degrees. At 0 degrees there is little reactivation of enzyme activity. However, in the presence of 0.2 M KCl containing 15 to 40% glycerol at 0 degrees, reactivation of the enzyme is about 50% complete. The rate of reactivation of enzyme in the presence of KCl or NADPH conforms to first order kinetics. This result suggests that the subunits first combine to form an inactive complex which is subsequently transformed to an enzymatically active complex. Evidence for the presence of inactive complex was obtained in experiments carried out in 0.2 M KCl at pH 6.0, and in 0.2 M KCl at pH 8.3, at both 6 and 3 degrees. Under these conditions the amount of complex observed upon ultracentrifugation was greater than expected from determinations of enzyme activity. The above findings suggest that ionic and hydrophobic interactions, and possibly the water structure surrounding the interacting sites, are of prime importance in reassociation and reactivation of enzyme. In addition, NADP+ and NADPH have very specific effects in bringing about reassociation and in maintaining the structural integrity of the multienzyme complex.


Associations of polymorphisms in the candidate genes for Alzheimer's disease BIN1, CLU, CR1 and PICALM with gestational diabetes and impaired glucose tolerance.
Alzheimer's disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called "type 3 diabetes mellitus". The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism-gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03-1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51-0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.


Caudatin blocks the proliferation, stemness and glycolysis of non-small cell lung cancer cells through the Raf/MEK/ERK pathway.
The antitumor effects of caudatin have been explored in multiple cancers, but the research on lung cancer has not been fully understood. We explored the effects of caudatin on non-small cell lung cancer (NSCLC) in vitro and in vivo. In the in vitro experiments, 0, 25, 50 and 100 μM of caudatin were selected to examine the effects on stemness and glycolysis. Subcutaneous tumour xenografts were constructed by injecting the nude mice (BALB/C) with 5 × 106 H1299 cells. In the in vivo experiments, all nude mice were divided into the caudatin group (50 mg/kg/day, n = 5) and the sham group (equal amount of DMSO, n = 5). The IC50 of caudatin for H1299 and H520 cells was 44.68 μM and 69.37 μM, respectively. Compared with caudatin 0 μM group, cell apoptosis rate was increased about 10 times and cell stemness was decreased by 75-85% in caudatin 100 μM group. Glucose uptake (65-80% reduction), lactic acid production (75-80% reduction), ATP level (70-80% reduction) and the expression of HK2 and LDHA (75-85% reduction) were decreased in caudatin 100 μM group. The expression of Raf/MEK/ERK pathway related proteins was decreased to 20-25% by caudatin. Tumour weight (about 70% reduction) and the expression of stemness, glycolysis and Raf/MEK/ERK pathway related proteins (about 50-75% reduction) were suppressed by caudatin in vivo. We revealed that caudatin blocked stemness and glycolysis in NSCLC for the first time. More experiments about exact dosage of caudatin in vivo should be conducted.


Detection of high-risk human papillomaviruses in fresh breast cancer samples using the hybrid capture 2 assay.
The etiology of breast cancer remains unknown and the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. This study investigated the prevalence of high-risk HPV infections in Chinese women with breast cancer and the possible relationship between high-risk HPV infection and the clinicopathological characteristics of breast cancer. Tumor cells from 224 fresh breast cancer samples and 37 fresh breast fibroadenomas were collected for hybrid capture 2 (HC2) assay. HC2 was the only technique approved by the United States Food and Drug Administration for screening for high-risk HPV infection in 2008. The prevalence of high-risk HPV infection in breast cancer samples was 21.4%, which was slightly higher than the 16.2% observed in breast fibroadenomas. Age and menopausal status were not risk factors for high-risk HPV infection among breast cancer patients. The clinical and pathological characteristics of breast cancer showed no significant correlation with high-risk HPV infection. Although the prevalence of 13 subtypes of high-risk HPV infections was similar in breast cancer and nonmalignant breast samples, the presence of high-risk HPVs in both malignant and benign breast samples implies that a possible causal role in breast cancer carcinogenesis could not be ruled out. Clarifying the possible link between high-risk HPVs and breast cancer might benefit women vaccinated against HPV and could decrease the incidence of HPV-related breast cancer.


Molecular pathology in real time.
With the development of sophisticated individualized therapeutic approaches, the role of pathology in classification of tumors is enormously increasing. The solely morphological characterization of neoplastic process is no more sufficient for qualified decision on optimal therapeutic approach. Thus, morphologic diagnosis must be supplemented by molecular analysis of the lesion with emphasis on the detection of status of certain markers used as predictive factors for targeted therapy. Both intrinsic and acquired types of intratumor heterogeneity have an impact at various moments of cancer diagnostics and therapy. The primary heterogeneity of neoplastic tissue represents a significant problem in patients, where only limited biopsy samples from the primary tumor are available for diagnosis, such as core needle biopsy specimens in breast cancer, transthoracic or endobronchial biopsies in lung cancer, or endoscopic biopsies in gastric cancer. Detection of predictive markers may be influenced by this heterogeneity, and the marker detection may be falsely negative or (less probably) falsely positive. In addition, as these markers are often detected in the tissue samples from primary tumor, the differences between molecular features of the primary lesion and its metastases may be responsible for failure of systemic therapy in patients with discordant phenotype between primary and metastatic disease. The fact of tumor heterogeneity must be taken into consideration already in establishing pathological diagnosis. One has to be aware that limited biopsy specimen must not always be fully representative of the entire tumor volume. To overcome these limitations, there does not exist one single simple solution. Examination of more tissue (preference of surgical resection specimens over biopsies, whenever possible), use of ultra-sensitive methods able to identify the minute subclones as a source of possible resistance to treatment, and detection of secondary molecular events from the circulating tumor cells or circulating cell-free DNA are potential solutions how to handle this issue.


Good Signal Detection Practices: Evidence from IMI PROTECT.
Over a period of 5 years, the Innovative Medicines Initiative PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) project has addressed key research questions relevant to the science of safety signal detection. The results of studies conducted into quantitative signal detection in spontaneous reporting, clinical trial and electronic health records databases are summarised and 39 recommendations have been formulated, many based on comparative analyses across a range of databases (e.g. regulatory, pharmaceutical company). The recommendations point to pragmatic steps that those working in the pharmacovigilance community can take to improve signal detection practices, whether in a national or international agency or in a pharmaceutical company setting. PROTECT has also pointed to areas of potentially fruitful future research and some areas where further effort is likely to yield less.


The use of novel water-in-oil microemulsions in microemulsion electrokinetic chromatography.
We describe the novel use of water-in-oil (W/O) microemulsions to achieve unique separations in microemulsion electrokinetic chromatography (MEEKC). The choice and concentration of the buffer type, surfactant and co-surfactant were all examined and optimized. Separations of a range of neutral and acidic analytes was shown to be markedly different to that obtained by (oil-in-water) O/W MEEKC. Neutral solutes are separated by virtue of their solubility (log P) values in O/W MEEKC with the more water-insoluble solutes migrating last. This separation process does not occur in W/O, as neutral solutes are not separated in order of log P.


Association of milk consumption with the incidence of cholelithiasis disease in the US adult population.
Cholelithiasis is a common digestive system disease that imposes major burden on patients and society. Investigating the relationship between dietary factors and cholelithiasis risk can provide a basis for disease prevention. Previous studies on milk intake and cholelithiasis incidence have been limited.Therefore, the aim of our study was to assess the association between milk consumption and the incidence of cholelithiasis in males and females. We selected 14,722 adults (≥ 18 years old) from National Center for Health Statistics (NHANSE) 2017-2020, and collected general characteristics of patients in the database, such as age, gender, race and body mass index (BMI), as well as dietary information (milk consumption). The occurrence of cholelithiasis was used as the outcome event, and the group was divided into cholelithiasis and non-cholelithiasis groups according to the outcome event. We used logistic regression models in generalized linear model (GLM) functions, controlling for demographic, lifestyle, and dietary factors, to estimate the association between milk intake and the incidence of cholelithiasis in males and females. A total of 14,722 adults were included. In the present study, the overall weighted prevalence of cholelithiasis was 10.96%, with 15.18% and 6.48% prevalence in females and males, respectively. Compared to infrequent milk intake, frequent milk intake (once a week or more) in females was associated with reduced cholelithiasis risk (OR 0.74, 95% CI 0.61-0.90). Daily milk intake in males was also related to lower cholelithiasis risk (OR 0.69-0.82). As adjusted variables increased in the models, predictive performance was improved (AUC 0.711 in females, 0.730 in males). Appropriate milk intake may correlate with decreased cholelithiasis risk. Our study provides a basis for dietary interventions against gallstones, but prospective studies are needed to verify the results.


Prosthodontic laboratory and curriculum survey. Part IV: Fixed prosthodontic curriculum survey.
A fixed prosthodontic curriculum survey was mailed to 60 U.S. dental schools; 42 surveys were returned. The results were compared with those of Part III of the study. Comparisons and their implications were discussed.


[Morphology of lymph vessels in human gastric carcinoma tissues and its association with cancer metastasis].
To investigate the morphology of the lymph vessels in human gastric carcinoma tissues and the relationship to cancer metastasis. Morphological changes of the lymph vessels and capillaries in 32 cases of gastric carcinoma tissues and adjacent tissue of the tumor. Numerous lymph vessels and capillaries were seen with opened lumen in the adjacent tissues of the tumor, and fasciculated lymph capillaries were most frequent in gastric carcinoma. The maximal lumen area, perimeter and diameter of lymph vessels and capillaries in gastric carcinoma and the adjacent tissues were significantly different between metastatic group and non-metastatic group (P<0.05). Dilation of lymph vessels and capillaries due to interstitial edema of the adjacent tissues of gastric carcinoma facilitates tumor metastasis, and lymph metastasis of carcinoma cells occurs through mature lymph capillaries in the adjacent tissues.


Direct determination of styrene-7,8-oxide in blood by gas chromatography with flame ionization detection.
A simple capillary gas chromatographic method is described for direct determination of styrene-7,8-oxide (styrene oxide) in blood samples of 1 ml, with a detection limit of 1 ng/ml. After the addition of 1-phenylpropylene oxide as internal standard, blood samples were extracted with n-hexane, the n-hexane phases were concentrated under nitrogen, and up to 25 microliters of the resulting solution were injected on-column using a retention gap. Separation was carried out on a fused-silica capillary column coupled to a flame ionization detector. Using this method the metabolism of styrene oxide in rat blood was investigated. Concentrations of styrene oxide in the blood of rats exposed to styrene at atmospheric concentrations between 20 and 800 ppm for 3 h at steady-state conditions are reported.


Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus.
To analyze cell lineage in the murine cerebral cortex, we infected progenitor cells with a recombinant retrovirus, then used the retroviral gene product to identify the descendants of infected cells. Cortices were infected on E12-E14 either in vivo or following dissociation and culture. In both cases, nearly all clones contained either neurons or glia, but not both. Thus, neuronal and glial lineages appear to diverge early in cortical development. To analyze the distribution of clonally related cells in vivo, clonal boundaries were reconstructed from serial sections. Perinatally (E18-PN0), clonally related cells were radially arrayed as they migrated to the cortical plate. Thus, clonal cohorts traverse a similar radial path. Following migration (PN7-PN23), neuronal clones generally remained radially arrayed, while glial clones were variable in orientation, suggesting that these two cell types accumulate in different ways. Neuronal clones sometimes spanned the full thickness of the cortex. Thus, a single progenitor can contribute neurons to several laminae.


Roles of specialized pro-resolving mediators and omega-3 polyunsaturated fatty acids in periodontal inflammation and impact on oral microbiota.
Periodontitis is a chronic inflammatory disease induced by dysbiotic dental biofilms. Management of periodontitis is primarily anti-bacterial via mechanical removal of bacterial biofilm. The successful resolution requires wound healing and tissue regeneration, which are not always achieved with these traditional methods. The discovery of specialized pro-resolving mediators (SPMs), a class of lipid mediators that induce the resolution of inflammation and promote local tissue homeostasis, creates another option for the treatment of periodontitis and other diseases of chronic inflammation. In this mini-review, we discuss the host-modulatory effects of SPMs on periodontal tissues and changes in the taxonomic composition of the gut and oral microbiome in the presence of SPMs and SPM precursor lipids. Further research into the relationship between host SPM production and microbiome-SPM modification has the potential to unveil new diagnostic markers of inflammation and wound healing. Expanding this field may drive the discovery of microbial-derived bioactive therapeutics to modulate immune responses.


Hugonella massiliensis gen. nov., sp. nov., genome sequence, and description of a new strictly anaerobic bacterium isolated from the human gut.
The human gut is composed of a large diversity of microorganisms, which have been poorly described. Here, using culturomics, a new concept based on the variation in culture conditions and MALDI-TOF MS identification, we proceed to explore the microbial diversity of the complex ecosystem of the human gut. Using this approach, we isolated strain AT8T (=CSUR P2118 = DSM 101782) from stool specimens collected from a 51-year-old obese French woman. Strain AT8T is a strictly anaerobic, nonmotile, nonspore-forming gram-positive coccus that do not exhibit catalase and oxidase activities. 16S rDNA-based identification of strain AT8T demonstrated 92% gene sequence similarity with Eggerthella lenta DSM 2243, the phylogenetically closed validly named type species. Here, we present a set of features for the strain AT8T and the description of its complete genome sequence and annotation. The 2,091,845 bp long genome has a G+C content of 63.46% and encodes1,849 predicted genes; 1,781 were protein-coding genes, and 68 were RNAs. On the basis of the characteristics reported here, we propose the creation of a new bacterial genus Hugonella gen. nov., belonging to the Eggerthellaceae family and including Hugonella massiliensis gen. nov., sp. nov., strain AT8T as the type strain.


Cross-reactive carbohydrate determinant-specific IgE obscures true atopy and exhibits ⍺-1,3-fucose epitope-specific inverse associations with asthma.
In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core β-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.


Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in bmx model mice.
There is no approved therapy for Becker muscular dystrophy (BMD), a genetic muscle disease caused by in-frame dystrophin deletions. We previously developed the dissociative corticosteroid vamorolone for treatment of the allelic, dystrophin-null disease Duchenne muscular dystrophy. We hypothesize vamorolone can treat BMD by safely reducing inflammatory signaling in muscle and through a novel mechanism of increasing dystrophin protein via suppression of dystrophin-targeting miRNAs. Here, we test this in the bmx mouse model of BMD. Daily oral treatment with vamorolone or prednisolone improves bmx grip strength and hang time phenotypes. Both drugs reduce myofiber size and decrease the percentage of centrally nucleated fibers. Vamorolone shows improved safety versus prednisolone by avoiding or reducing key side effects to behavior and growth. Intriguingly, vamorolone increases dystrophin protein in both heart and skeletal muscle. These data indicate that vamorolone, nearing approval for Duchenne, shows efficacy in bmx mice and therefore warrants clinical investigation in BMD.