Protective effects of melatonin on testis histology following acute torsion-detorsion in rats.
Testicular damage due to spermatic cord torsion may lead to infertility. It is probably because of changes in oxidative stress factors such as malondialdehyde. To investigate the protective effect of melatonin (MLT), as an antioxidant, on testicular damage induced by acute unilateral spermatic cord torsion and detorsion (T/D) in rats. In this experimental study, 48 adult male Wistar rats were randomly divided into three groups (8 rats/group): sham group underwent right scrotal surgery only., the T/D group underwent right testicular torsion (for 1 hr) and detorsion, and the melatonin group underwent right testicular torsion, received 25 µg/kg melatonin intraperitoneally immediately after surgery of T/D. Then the histological parameters and malondialdehyde (MDA) changes were evaluated. Torsion and detorsion decreased the diameter of the tubules significantly compared to controls (p=0.003). Melatonin could increase the diameter, but it was not significant (p=0.26). The heights of the epithelium were constant in sham, T/D, and melatonin groups without any significant difference between groups (p=0.98). Based on Johnsen's score, spermatogenesis was normal in the sham group. The torsion significantly injured all lineage cells (p<0.001). There was no any spermatid or sperm in the seminiferous tubules. Melatonin improved the spermatogenesis significantly (p=0.02), but could not improve MDA level significantly (p=0.99). Severe degenerative changes of testis were induced by acute unilateral spermatic cord torsion and detorsion in rats, but it had no effect on MDA level.


The maxillary ameloblastoma: an analysis of 24 cases.
Twenty-four cases of maxillary ameloblastoma from the files of the dental and oral division of the Armed Forces Institute of Pathology and the US Army Institute of Dental Research were reviewed. Clinical findings showed an average age of 45.6 years, a male-to-female ratio of 2.4:1, and an equal racial distribution between whites and blacks. Eighty-eight percent of the tumors occurred distal to the maxillary canine. A slowly enlarging mass was the primary clinical sign in more than 90% of the cases. Recurrences were seen in eight of the 16 cases on which follow-up information was received. The majority of the tumors had a mixed follicular histologic pattern. Therapy should consist of either surgical block excision or hemimaxillectomy. The surgeon must carefully weigh the potential danger of the neoplasm against the deformity and disability caused by the surgical procedure.


Echocardiographic parameters to predict inadequate defibrillation safety margin in patients receiving implantable cardioverter defibrillators for primary prevention.
Implantable cardioverter defibrillators (ICDs) have become an important part of the management of patients with congestive heart failure. At the time of ICD implantation, ventricular fibrillation (VF) is induced to assess adequate energy required for defibrillation. There are multiple parameters which influence the defibrillation safety margin (DSM); however, these factors are not well-established when ICDs are implanted for the primary prevention of sudden cardiac death (SCD) in patients with severe systolic dysfunction. We evaluated multiple clinical and echocardiographic parameters as predictors of adequate DSM in patients referred for ICD implantation for the primary prevention of SCD. We prospectively enrolled 41 patients for ICD implantation with clinical indications for the primary prevention of SCD. Two blinded independent readers evaluated the prespecified echocardiographic parameters. These included left ventricular (LV) mass, indices of right ventricular and LV systolic and diastolic functions, and LV geometric dimensions. Basic clinical demographics, including age, gender, comorbidities, and etiology of cardiomyopathy, were also evaluated. DSM was established using our standard protocol for defibrillation testing which includes VF with successful first shock terminating VF at a value at least 10 J below the maximum output of the implanted device. High defibrillation thresholds (DFT) were defined as >21 J. The mean age is 61.8 ± 14.7 years, with men comprising the majority of the patients (73 %). The only clinical variables which predicted the high DFT were age (in years) (54.5 ± 17.5 vs. 65.7 ± 11.3, p = 0.044), QRS duration (in milliseconds) (116.0 ± 29.5 vs. 110.5 ± 21.8, p = 0.03), LV mass (in grams) (241.0 ± 77.9 vs. 181.9 ± 52.3, p = 0.006), and LV mass index (in grams per square meter) (111.1 ± 38.2 vs. 86.4 ± 21.1, p = 0.02). On multivariate logistic regression analysis, LV mass was the only independent predictor of low DFT (≤22 J) in patients with ICD implanted for the primary prevention of SCD. LV mass may help predict an adequate DSM in patients who are referred for ICD implantation for the primary prevention of SCD. These results may help distinguish the patients who may require high-energy devices prior to the implantation procedure. These results may help distinguish patients requiring high-energy devices, coils, or advanced programming prior to implantation and appropriate referral to electrophysiologists.


Temporal variation in individual factors associated with hantavirus infection in bank voles during an epizootic: implications for Puumala virus transmission dynamics.
Puumala virus (PUUV), the causal agent of nephropathia epidemica in humans, is one of the many hantaviruses included in the list of emerging pathogens. Hantavirus infection is not distributed evenly among PUUV reservoir hosts (i.e., bank voles [Myodes glareolus]). Besides environmental factors and local population features, individual characteristics play an important role in vole PUUV infection risk. Identifying the relative importance of these individual characteristics can provide crucial information on PUUV transmission processes. In the present study, bank voles were monitored during the nephropathia epidemica outbreak of 2005 in Belgium. Vole sera were tested for presence of immunoglobulin G against PUUV, and a logistic mixed model was built to investigate the temporal variation in individual characteristics and their relative importance to PUUV infection risk in bank voles. Relative risk calculations for individual vole characteristics related to PUUV infection in the reservoir host show that reproductive activity dominates infection risk. The gender effect is only found in reproductively active voles, where reproductively active males have the highest infection risk. Results also revealed a clear seasonal variation in the importance of reproductive activity linked to PUUV infection. In contrast to the main effect found in other trapping sessions, no difference in infection risk ratio was found between reproductively active and nonactive voles in the spring period. Combined with increased infection risk for the reproductively nonactive group at that time, these results indicate a shift in the transmission process due to changes in bank vole behavior, physiology, or climate conditions. Hence, our results suggest that mathematical models should take into account seasonal shifts in transmission mechanisms. When these results are combined with the seasonal changes in population structure during the epizootic period, we identify vole reproductive activity and length of the breeding season as potential drivers of PUUV epizootics in west-central European regions.


Experience of hospital-initiated medication changes in older people with multimorbidity: a multicentre mixed-methods study embedded in the OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial.
A patient-centred approach to medicines optimisation is considered essential. The OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial evaluated the effectiveness of medication review with shared decision-making (SDM) in older people with multimorbidity. Beyond evaluating the clinical effectiveness, exploring the patient experience facilitates a better understanding of contextual factors and mechanisms affecting medication review effectiveness. To explore experiences of hospital-initiated medication changes in older people with multimorbidity. We conducted a multicentre mixed-methods study, embedded in the OPERAM trial, combining semi-structured interviews and the Beliefs about Medicines Questionnaire (BMQ) with a purposive sample of 48 patients (70-94 years) from four European countries. Interviews were analysed using the Framework approach. Trial implementation data on SDM were collected and the 9-item SDM questionnaire was conducted with 17 clinicians. Patients generally displayed positive attitudes towards medication review, yet emphasised the importance of long-term, trusting relationships such as with their general practitioners for medication review. Many patients reported a lack of information and communication about medication changes and predominantly experienced paternalistic decision-making. Patients' beliefs that 'doctors know best', 'blind trust', having limited opportunities for questions, use of jargon terms by clinicians, 'feeling too ill', dismissive clinicians, etc highlight the powerlessness some patients felt during hospitalisation, all representing barriers to SDM. Conversely, involvement of companions, health literacy, empathetic and trusting patient-doctor relationships, facilitated SDM. Paradoxical to patients' experiential accounts, clinicians reported high levels of SDM. The BMQ showed that most patients had high necessity and low concern beliefs about medicines. Beliefs about medicines, experiencing benefits or harms from medication changes, illness perception, trust and balancing advice between different healthcare professionals all affected acceptance of medication changes. To meet patients' needs, future medicines optimisation interventions should enhance information exchange, better prepare patients and clinicians for partnership in care and foster collaborative medication reviews across care settings.


The Validity and Reliability of Malay Version Child Exposure to Domestic Violence Scale.
Domestic violence has a significant impact on growing children. However, existing evidence is limited and often under reported. Consequently, the Child Exposure to Domestic Violence (CEDV) scale has been developed for global use. This study aims to provide a cross-cultural translation, adaptation and validation of the CEDV based on Malay language. CEDV scale was translated from the original English version to Malay. Content and face validity were examined before field-testing. The study comprised a cross sectional study using the Malay version of the CEDV (CEDV-M) scale conducted at a secondary school in Perlis, Malaysia and investigated 235 children aged 13 years old-16 years old using an online platform. The construct validity, internal consistency and stability of the tool were assessed. The CEDV-M scale's content and face validity both yielded a value exceeding 0.80. Furthermore, the tool demonstrated has good stability reliability, using the intra-class correlation value for all items ranging from 0.659 to 1.00. The exploratory factor analysis of the 36 items of the CEDV scale revealed possibilities of five or six factor domains. However, the five factor domains were most conceptually equivalent. Consequently, this study found that the CEDV-M scale is reliable with a total Cronbach's alpha of 0.87. CEDV-M scale is a valid and reliable tool for measuring a child's experience of domestic violence. Future studies recommend confirmatory factor analysis and standard settings for scoring systems.


Structural proteins of mammalian oncogenic RNA viruses: multiple antigenic determinants of the major internal protein and envelope glycoprotein.
The antigenic determinants of two purified protein constituents of mammalian C-type RNA viruses, the major structural protein of about 30,000 daltons, and the membrane glycopeptides of about 70,000 daltons were examined by competition radioimmunoassay. By the appropriate choice of antiserum and competing proteins, it was possible to distinguish type-specific, group-specific, and interspecies determinants. Both of the viral constituents were found to contain each of these three classes of antigens. The results suggested that the majority of the determinants of the major structural protein were group specific, 5% to 30% were interspecies, and a small fraction were type specific. In the case of the envelope glycopeptides, the chief determinants were type and group specific, and a small fraction were interspecies.


The role of bone marrow microenvironment in platelet production and their implications for the treatment of thrombocytopenic diseases.
Impaired platelet production has been found to be an important pathological mechanism of thrombocytopenia in many diseases. Platelet generation is a complex process that mainly occurs in the bone marrow, and thus is closely regulated by the bone marrow microenvironment. This review attempts to summarize the most current knowledge referring the role of bone marrow microenvironment in the regulation of platelet production. The effects of multiple microenvironment ingredients in regulating megakaryopoiesis and thrombocytopoiesis have been discussed. Abnormalities of these components in thrombocytopenic diseases are also described. Thrombocytopenia is a common clinical manifestation of a variety of diseases. The functional importance of platelets has driven the developments of a broad range of studies. Platelet generation mainly occurs within the bone marrow, where the cells, soluble factors, and extracellular matrix proteins collaboratively form a complex regulatory network, directing megakaryocytic proliferation and differentiation. Alteration in any part of the regulating network may result in defective platelet formation, and eventually lead to thrombocytopenia. A variety of thrombocytopenic diseases have been found to be related with the disregulated bone marrow microenvironment. Identification of the variations of these niche ingredients in certain diseases has facilitated the developments of multiple therapeutic regimes. Further studies that can combine these niche factors with their downstream regulatory factors will be beneficial for developing more effective therapies. Further definition of the role of bone marrow microenvironment in platelet generation may deepen our understanding of the underlying mechanisms as well as provide new therapeutic targets for thrombocytopenic diseases.


Inhibition of DNA replication by ultraviolet light.
DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10J/m2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers.


[Blood levels of Fe, Zn, Br and Rb determined by radionuclide x-ray fluorescence analysis in patients with dilated cardiomyopathy].
In 68 patients (50 men between the age of 18-59, 18 women between the age of 20-53) inflicted by dilatation cardiomyopathy in the stage of severe decompensation (functional NYHA group III-IV, the concentrations of Fe, Zn, Br, and Rb in whole blood were determined by means of radionuclide X-ray-fluorescence analysis. The Fe concentration (X = 401.26 +/- 14.58) was significantly lower (alpha = 0.074), the Zn concentration (X = 8.20 +/- 0.95) was not significantly altered, the trace elements concentration Br (X = 32.30 +/- 4.61) and Rb (X = 4.58 +/- 0.38) were remarkably and significantly higher (alpha = 2.10(-16), resp. alpha < or = 1.10(-16)) when compared with concentrations of these elements in healthy controls. The method of radionuclide X-ray-fluorescence analysis is suitable for element analysis of blood. Its advantages reside in its rapidness, polycomponence, sample nondestructiveness and low requirement of material. (Tab. 3, Fig. 4, Ref. 17.)


[Mitochondrial genetics and human essential hypertension].
Mitochondrial DNA (mtDNA) exhibits matrilineal inherence. Familial mitochondrial diseases caused by mtDNA mutations are generally involved in organs featuring high energy consumption, which include heart, brain and skeletal muscle. Recently, it has been found that some essential hypertension patients featured classical maternal inheritance, which has confirmed and enriched mtDNA mutations as one of the molecular mechanisms underlying maternally inherited hypertension. Nevertheless, more general as well as radical questions are still to be answered. This article reviews recent advance in mitochondrial genome evolution, mtDNA genetics and the role of mtDNA mutations in maternally inherited hypertension.


Circulatory responses in children with unexplained syncope evaluated by continuous non-invasive finger blood pressure monitoring.
Cardiovascular responses on active standing in children with unexplained syncope were investigated with continuous non-invasive finger artery pressure monitoring (Finapres). We examined 34 symptomatic patients (13 boys and 21 girls), aged 8-16 years, and 24 age-matched controls. Finger blood pressure and heart rate were monitored continuously for 5 min in the supine position and for 10 min while standing. Ten of 34 patients developed fainting symptoms with hypotension during upright posture (fainters). In the initial standing phase (0-30 s), two prominent abnormal blood pressure responses were found in patients: a marked decrease 45 +/- 18/23 +/- 8 mmHg and a prolonged recovery time (16.5 +/- 2.9 versus 27.7 +/- 13.6 s), which appeared to be based on impaired vasoconstriction. Either or both abnormalities were observed in 21 (62%) of the 34 patients and in 2 (8%) of the controls. In addition, fainters also had a more marked increase in heart rate during standing compared with non-fainters. Our findings suggested that more than half of children with syncope had abnormal cardiovascular reflexes in the initial phase which appeared to be associated with vasodepressor syncope. The active standing test with a continuous beat-to-beat blood pressure recording has a high sensitivity in detecting abnormalities of autonomic function in patients with unexplained syncope.


Intrasellar pituitary tissue pressure, tumour size and endocrine status--an international comparison in 107 patients.
In a two-centre study, intrasellar pituitary tissue pressure was measured at transsphenoidal surgery in 107 patients with pituitary adenomas or intrasellar cysts. 'Normal' ISP in patients under anaesthesia with small microadenomas (< 5 mm diameter) or a partial empty sella was 12 +/- 3 mmHg. Raised ISP (> 15 mmHg) was found in 75% of cases. The highest pressures were recorded in tumours with parasellar invasion (30 +/- 2; p < 0.01) irrespective of size and extension in other directions. In non-invasive lesions there was no correlation between the level of raised ISP and tumour size. Hypopituitarism and stalk compression syndrome were both associated with higher ISP than patients with normal pituitary function.


Detailed characterization of antibody responses against HIV-1 group M consensus gp120 in rabbits.
We recently reported induction of broadly neutralizing antibodies (bnAbs) against multiple HIV-1 (human immunodeficiency virus type 1) isolates in rabbits, albeit weak against tier 2 viruses, using a monomeric gp120 derived from an M group consensus sequence (MCON6). To better understand the nature of the neutralizing activity, detailed characterization of immunological properties of the protein was performed. Immunogenic linear epitopes were identified during the course of immunization, and spatial distribution of these epitopes was determined. Subdomain antibody target analyses were done using the gp120 outer domain (gp120-OD) and eOD-GT6, a protein based on a heterologous sequence. In addition, refined epitope mapping analyses were done by competition assays using several nAbs with known epitopes. Based on linear epitope mapping analyses, the V3 loop was most immunogenic, followed by C1 and C5 regions. The V1/V2 loop was surprisingly non-immunogenic. Many immunogenic epitopes were clustered together even when they were distantly separated in primary sequence, suggesting the presence of immunogenic hotspots on the protein surface. Although substantial antibody responses were directed against the outer domain, only about 0.1% of the antibodies bound eOD-GT6. Albeit weak, antibodies against peptides that corresponded to a part of the bnAb VRC01 binding site were detected. Although gp120-induced antibodies could not block VRC01 binding to eOD-GT6, they were able to inhibit VRC01 binding to both gp120 and trimeric BG505 SOSIP gp140. The immune sera also efficiently competed with CD4-IgG2, as well as nAbs 447-52D, PGT121 and PGT126, in binding to gp120. The results suggest that some antibodies that bind at or near known bnAb epitopes could be partly responsible for the breadth of neutralizing activity induced by gp120 in our study. Immunization strategies that enhance induction of these antibodies relative to others (e.g. V3 loop), and increase their affinity, could improve protective efficacy of an HIV-1 vaccine.


Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival.
Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a "converted" subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.


Somatic cell nuclear transfer in mammals: progress and applications.
Somatic nuclear transfer has been performed with frogs since the early 1960s, yet it has proved impossible to generate an adult frog using an adult cell as nuclear donor. After some initial skepticism, the birth of sheep, cows, goats, and mice using this technique with fetal or adult cell donors is now established fact. The success with adult mammalian cell donors extends the historic work in frogs by attesting to the totipotency of nuclei in at least some adult, differentiated cell types. Because the technique offers a developmental read out of the totality of genetic and molecular lifetime changes accumulated by the nucleus of a single somatic cell, basic research applications are seen in the fields of ageing, cancer, X chromosome inactivation, and imprinting. The prospect of a method for gene targeting in livestock holds particular promise for commercial applications; whilst for humans, the use of nuclear transfer to provide diverse populations of customized stem cells for therapeutic purposes presents a tantalizing future goal.


Early removal of urinary catheter after excision and primary anastomosis in anterior urethral stricture.
To investigate the feasibility of removing the urinary catheter 7 days after excision and primary anastomosis (EPA) performed with the indication of anterior urethral stricture disease. Retrospective review of medical records of the patients who had undergone EPA between January 2005 and December 2010 was performed. These patients were divided into 2 groups: Group 1 (urethral catheter removed on or before 7. postoperative day) and Group 2 (urethral catheter removed on 8. postoperative day or later). We compared 2 groups as for the frequency of extravasation as detected on retrograde pericatheter urethrogram (PUG) and recurrence rate till the last follow-up. PUG was performed on an average day 7 and 14 in Groups 1 (n=102) and 2 (n=134), respectively followed by removal of the catheter. Extravasation on the first PUG was detected in 6.8% of the patients in Group 1, and in 4.5% of the cases in Group 2 had extravasation on the first PUG. Urethral catheter was left in situ in these patients and a repeat PUG after one week was performed which was normal in all cases. The incidence of extravasation and recurrence rate did not differ significantly whether catheter was removed on day 7 or 14 (6.8% vs. 4.5% and 4.9% vs. 5.2% respectively) (p>0.5). We conclude that removal of the catheter on postoperative day 7 after EPA does not increase the rate of extravasation and recurrence during long-term follow-up. Urethral catheter restricts physical activity in the postoperative period which is bothersome to the patient. Hence early removal of a catheter should be offered to men after EPA.


The synthesis and structure of heteroleptic tris(diimine)ruthenium(II) complexes.
The reactions of bidentate diimine ligands (L2) with cationic bis(diimine)[Ru(L)(L1)(CO)Cl]+ complexes (L, L1, L2 are dissimilar diimine ligands), in the presence of trimethylamine-N-oxide (Me3NO) as a decarbonylation reagent, lead to the formation of heteroleptic tris(diimine) ruthenium(II) complexes, [Ru(L)(L1)(L2)]2+. Typically isolated as hexafluorophosphate or perchlorate salts, these complexes were characterised by UV-visible, infrared and mass spectroscopy, cyclic voltammetry, microanalyses and NMR spectroscopy. Single crystal X-ray studies have elucidated the structures of K[Ru(bpy)(phen)(4,4'-Me(2)bpy)](PF(6))(3).1/2H(2)O, [Ru(bpy)(5,6-Me(2)phen)(Hdpa)](ClO(4))(2), [Ru(bpy)(phen)(5,6-Me(2)phen)](ClO(4))(2), [Ru(bpy)(5,6'-Me(2)phen)(4,4'-Me(2)bpy)](PF(6))(2).EtOH, [Ru(4,4'-Me(2)bpy)(phen)(Hdpa)](PF(6))(2).MeOH and [Ru(bpy)(4,4'-Me(2)bpy)(Hdpa)](ClO(4))(2).1/2Hdpa (where Hdpa is di(2-pyridyl)amine). A novel feature of the first complex is the presence of a dinuclear anionic adduct, [K(2)(PF(6))(6)](4-), in which the two potassium centres are bridged by two fluorides from different hexafluorophosphate ions forming a K(2)F(2) bridging unit and by two KFPFK bridging moieties.


Human papilloma viruses in the human hypopharynx.
The possible association of human papilloma viruses (HPV) with laryngopharyngeal squamous cell carcinoma is under investigation. Recent work suggests regional differences in the prevalence of HPV infection in the hypopharynx. The present study investigates the prevalence of HPV in tissue obtained from a series of piriform fossae. Piriform fossa epithelium was harvested from 12 autopsy cases free of local disease. DNA was obtained by SDS/Proteinase K digestion. Evidence of HPV infection was documented by the polymerase chain reaction using oligonucleotide primers complementary to sequences in the E6 region of HPV types 11, 16 and 18. All the specimens were positive for beta-globin. HPV11 was isolated from two patients. None were positive for HPV16 or HPV18. An 18% prevalence rate for HPV11 in the normal human hypopharynx was found.


Targeting of myelin protein zero in a spontaneous autoimmune polyneuropathy.
Elimination of the costimulatory molecule B7-2 prevents autoimmune diabetes in NOD mice, but leads to the development of a spontaneous autoimmune polyneuropathy (SAP), which resembles the human disease chronic inflammatory demyelinating polyneuropathy (CIDP). In this study, we examined the immunopathogenic mechanisms in this model, including identification of SAP Ags. We found that B7-2-deficient NOD mice exhibit changes in cytokine and chemokine gene expression in spleens over time. There was an increase in IL-17 and a decrease in IL-10 transcript levels at 4 mo (preclinical phase), whereas IFN-gamma expression peaked at 8 mo (clinical phase). There was also an increase in transcript levels of Th1 cytokines, CXCL10, and RANTES in sciatic nerves of mice that developed SAP. Splenocytes from SAP mice exhibited proliferative and Th1 cytokine responses to myelin P0 (180-199), but not to other P0 peptides or P2 (53-78). Adoptive transfer of P0-reactive T cells generated from SAP mice induced neuropathy in four of six NOD.SCID mice. Data from i.v. tolerance studies indicate that myelin P0 is one of the autoantigens targeted by T cells in SAP in this model. The expression of P0 by peri-islet Schwann cells provides a potential mechanism linking islet autoimmunity and inflammatory neuropathy.


Enhancing the quality of phylogenetic analysis using fuzzy hidden Markov model alignments.
Any effective phylogeny inference based on molecular data begins by performing efficient multiple sequence alignments. So far, the Hidden Markov Model (HMM) method for multiple sequence alignment has been proved competitive to the classical deterministic algorithms with respect to phylogenetic analysis; nevertheless, its stochastic nature does not help it cope with the existing dependence among the sequence elements. This paper deals with phylogenetic analysis of protein and gene data using multiple sequence alignments produced by fuzzy profile Hidden Markov Models. Fuzzy profile HMMs are a novel type of profile HMMs based on fuzzy sets and fuzzy integrals, which generalize the classical stochastic HMM by relaxing its independence assumptions. In this paper, alignments produced by the fuzzy HMM model are used in phylogenetic analysis of protein data, enhancing the quality of phylogenetic trees. The new methodology is implemented in HPV virus phylogenetic inference. The results of the analysis are compared against those obtained by the classical profile HMM model and depict the superiority of the fuzzy profile HMM in this field.


In vitro targeted screening and molecular docking of stilbene, quinones, and flavonoid on 3T3-L1 pre-adipocytes for anti-adipogenic actions.
In metabolic disorders like obesity, NAFLD and T2DM, adipocytes are dysfunctional. Hence, pharmacological interventions have importance in preventing differentiation of adipocytes and stimulating lipid uptake. We, therefore, investigated the effects of arbutin (ARB), purpurin (PUR), quercetin (QR), and pterostilbene (PTS) on adipocyte differentiation and lipid uptake using 3T3-L1 adipocytes. Further, in silico docking studies were achieved to investigate interactions of ARB, PUR, QR, and PTS with beta-ketoacyl reductase (KR) and thioesterase (TE) domains of fatty acid synthase (FAS) enzyme. Mature 3T3-L1 adipocytes were used to investigate the anti-adipogenic effect of selected pharmacological agents by Oil Red O staining and in vitro fatty acid uptake analysis. Molecular docking studies were performed to predict the binding interactions of selected compounds with KR and TE domains of FAS enzyme. All these agents significantly decrease the adipocyte differentiation and showed the stimulatory effect on fatty acid uptake in 3T3-L1 adipocytes. However, PTS and PUR proved to be anti-adipogenic, whereas ARB and QR showed significant effect on fatty acid uptake, compared to others. Similarly, all the compounds displayed significant binding interactions with KR and TE domains of FAS enzyme, supporting the results of in vitro studies. Graphical abstract.


Awareness, acceptability and uptake of cervical cancer vaccination services among female secondary school teachers in Enugu, Nigeria: a cross-sectional study.
cervical cancer is a major cause of morbidity and mortality in women and vaccination of adolescents with human papilloma virus (HPV) vaccines is a major preventive strategy for this cancer. Despite the usefulness of cervical cancer vaccines, significant gaps still exist in the level of awareness and acceptability of the vaccine among women. This study aimed to determine the level of awareness, acceptability, and identify the factors associated with the uptake of this vaccine by female secondary school teachers in Enugu, Nigeria. a cross-sectional study of 377 female teachers in Enugu metropolis was undertaken between July and October 2017. A structured interviewer-administered pretested questionnaire was used for data collection and SPSS used for analysis. less than half (41.9%) of the respondents had good knowledge of the cervical cancer vaccine. The majority of the respondents (93.6%) accepted the vaccine and will recommend it for their children and students. Only 14.6% and 9.0% of the respondents have taught their students about cervical cancer or HPV vaccines and had a programme in their school that addresses cervical cancer or cervical cancer vaccination respectively. Only 3.4% of the respondents have been vaccinated while 5.6% of their children or relatives have received the HPV vaccine. Previous vaccination of participants (p = 0.000), existing programmes addressing cervical cancer in schools of respondents (p = 0.000), participants having taught students about cervical cancer (p = 0.025) and high economic status (p = 0.013) significantly increased the likelihood of participants vaccinating their adolescent daughters/relatives. Extremes of age (p = 0.001) and being the head of their families (p = 0.002) significantly reduced the likelihood of the daughters/relatives to be vaccinated. Only previous history of vaccination of the respondents predicted the vaccination of their children and relatives (AOR = 6.069; 95% CI; < 0.0001-0.041). the overall knowledge of the HPV vaccine was low but the acceptability was high among respondents who were aware of the vaccines. Vaccine uptake among children/family members of the respondents was low. The introduction of cervical cancer vaccination education of the teachers in the secondary schools will help improve cervical cancer vaccination and the uptake among adolescent´s populations in the country.


Engineering Electromagnetic Hot-Spots in Nanoparticle Cluster Arrays on Reflective Substrates for Highly Sensitive Detection of (Bio)molecular Analytes.
Intense electromagnetic (EM) hot-spots arising at the junctions or gaps in plasmonic nanoparticle assemblies can drive ultrahigh sensitivity in molecular detection by surface-enhanced spectroscopies. Harnessing this potential however requires access to the confined physical space at the EM hot-spots, which is a challenge for larger analytes such as biomolecules. Here, we demonstrate self-assembly derived gold nanoparticle cluster arrays (NCAs) on gold substrates exhibiting controlled interparticle (<1 nm wide) and intercluster (<10 nm wide) hot-spots as highly promising in this direction. Sensitivity of the NCAs toward detection of small (<1 nm) or large (protein-receptor interactions) analytes in surface-enhanced Raman and metal-enhanced fluorescence assays is found to be strongly impacted by the size of the cluster and the presence of reflective substrates. Experiments supported by numerical simulations attribute the higher sensitivity to higher EM field enhancements at the hot-spots, as well as greater analyte leverage over EM hot-spots. The best-performing arrays could push the sensitivity down to picomolar detection limits for sub-nanometric organic analytes as well as large protein analytes. The investigation paves the way for rational design of plasmonic biosensors and highlights the unique capabilities of a molecular self-assembly approach toward catering to this objective.


Palladium(I)-Iodide-Catalyzed Deoxygenative Heck Reaction of Vinyl Triflates: A Formate-Mediated Cross-Electrophile Reductive Coupling with cine-Substitution.
The first deoxygenative Heck reactions are described, as illustrated by formate-mediated cine-substitutions of vinyl triflates with aryl iodides. The collective data corroborate a mechanism in which Pd(OAc)2 and Bu4NI form the dianionic iodide-bridged dimer [Pd2I6][NBu4]2, which, under reducing conditions, serves as a precursor to the palladium(I) complex [Pd2I4][NBu4]2. Dinculear oxidative addition of aryl iodide forms [Pd2I5(Ar)][NBu4]2, which dissociates to the monometallic complex [PdI2(Ar)][NBu4]. Vinyl triflate migratory insertion-sulfonate elimination delivers a palladium(IV) carbene, which upon β-hydride elimination/C-H reductive elimination gives the product of cine-substitution. These processes are the first efficient formate-mediated cross-electrophile reductive couplings beyond carbonyl addition.


Plate-like osteoma cutis.
Osteoma cutis is the aberrant development of bone within the skin. The bone formation may be de novo (primary) or result from an injury to the skin (secondary). Here we present a healthy 53-year-old man with no known abnormalities in calcium or phosphate metabolism with plate-like osteoma cutis of the scalp. Plate- or plaque-like osteoma cutis was initially described as a congenital condition but has now been reported several times in the literature as an idiopathic process that occurs in adults. Treatment options are limited and are only required if the lesion is bothersome to the patient.


Massive Right Chylothorax Secondary to a Severe Systemic Lupus Erythematosus Flare With Secondary Evans Syndrome: A Case Report and Literature Review.
This case report describes a 23-year-old male patient who presented with right chylothorax as the initial manifestation of a severe flare of systemic lupus erythematosus (SLE) and secondary Evans syndrome. Chylothorax and chylous ascites are rare features of SLE that can occur due to the accumulation of triglyceride-rich fluid in serous cavities. However, they have never been reported as the initial manifestation of a lupus flare. Evans syndrome is a rare disease characterized by autoimmune hemolytic anemia and immune thrombocytopenia, which can be secondary to SLE. The concomitant occurrence of both chylothorax and Evans syndrome in the setting of systemic lupus erythematosus has never been described, and the exact causative mechanisms of both entities are yet to be fully understood. In this report, we discuss our approach to this challenging case to broaden the understanding of the clinical manifestations of systemic lupus erythematosus. Our findings emphasize the importance of considering rare features of systemic lupus erythematosus and secondary diseases when evaluating patients with the disease.


Anthropological study of dental indices in Bulgarian population.
A number of derived quantities (called dental indices) that characterize the shape and size of the teeth are calculated between the absolute dimensions of the teeth (mesiodistal, vestibulo-oral, and height of the dental crown).


BF3-Promoted Divergent Reactions between Tryptophols and Propargylic Alcohols.
Trifluoroboron-promoted cascade reactions between tryptophols and propagylic alcohols furnished three types of skeletons, including carbazoles, cyclopenta[b]furo[2,3-b]indoles, and allenyl furo[2,3-b]indoles, with excellent selectivity based on the substrate structure. Tryptophols without a substituent on the 2-position of the indole ring reacted with 1,1,3-triphenylprop-2-yn-1-ol and 9-(phenylethynyl)-9H-fluoren-9-ol to give carbazoles and cyclopenta[b]furo[2,3-b]indoles, respectively, while the reaction of 2-substituted tryptophols afforded allenylfuro[2,3-b]indoles.


Quality of life in children and adolescents with bipolar I depression treated with olanzapine/fluoxetine combination.
We examined the efficacy of olanzapine/fluoxetine combination (OFC) in improving health-related quality of life (QoL) in the treatment of bipolar depression in children and adolescents. Patients aged 10-17 years with bipolar I disorder, depressed episode, baseline children's depression rating scale-revised (CDRS-R) total score ≥40, Young Mania Rating Scale (YMRS) total score ≤15, and YMRS-item 1 ≤ 2 were randomized to OFC (6/25-12/50 mg/day olanzapine/fluoxetine; n = 170) or placebo (n = 85) for up to 8 weeks of double-blind treatment. Patients and parents completed the revised KINDL questionnaire for measuring health-related QoL in children and adolescents (KINDL-R) at baseline and endpoint. The mean change in CDRS-R total and item scores were used to compare improvement in symptomatology in patients taking OFC and placebo. Tests were 2-sided using a Type I error cutoff of 0.05, and no adjustments for multiple comparisons were made. Baseline QoL as measured by the KINDL-R was substantially impaired relative to published norms for a healthy school-based sample. OFC-treated patients demonstrated an improvement over placebo at endpoint with respect to mean change from baseline in the patient-rated KINDL-R Self-esteem subscale score (p = 0.028), and in the parent KINDL-R ratings of emotional well-being (p = 0.020), Self-esteem (p = 0.030), and Family (p = 0.006). At endpoint, OFC-treated patients still had a lower QoL compared to the normative population. OFC showed significant improvement (p ≤ 0.05) versus placebo on the CDRS-R total score and on 7 of the 17 CDRS-R items. Patients aged 10-17 years with an acute episode of bipolar depression and their parents reported greater improvements (parents noticed improvements in more areas than did their offspring) on some aspects of QoL when treated with OFC compared with placebo. However, after 8 weeks of treatment, KINDL-R endpoint scores remained lower than those of the, presumably healthy, control population. Clinical trial registration information A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar Depression; http://www.clinicaltrials.gov; NCT00844857.


A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors, Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1.
Neurofibromatosis type 1 (NF1), also called von Recklinghausen's disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2). Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed.


Assessment of the National Library of Medicine's health disparities plan: a focus on Native American outreach.
Overcoming health disparities between majority and minority populations is a significant national challenge. This paper assesses outreach to Native Americans (American Indians, Alaska Natives, and Native Hawaiians) by the National Library of Medicine (NLM). A companion paper details NLM's portfolio of Native American outreach projects. NLM's Native American outreach is assessed in light of the presentations at a community-based health information outreach symposium and the goals set by NLM's plan to reduce health disparities. NLM's current portfolio of Native American outreach projects appears most advanced in meeting the goal set in area 1 of the health disparities plan, "Promote use of health information by health professionals and the public." NLM's portfolio also shows significant strength and good progress regarding area 2 of the plan, "Expand partnerships among various types of libraries and community-based organizations." The portfolio is weaker in area 3, "Conduct and support informatics research." More knowledge-building efforts would benefit NLM, the National Network of Libraries of Medicine, and Native American and community-based organizations. The current Native American outreach portfolio should be continued, but new approaches are needed for evaluating Native American outreach and for forging collaborations with Native American groups, approaches grounded in consultation and mutual understanding of needs and perspectives.


Severe Preeclampsia in the Setting of Myasthenia Gravis.
Myasthenia gravis (MG) is a rare autoimmune disease that leads to progressive muscle weakness and is common during female reproductive years. The myasthenic mother and her newborn must be observed carefully, as complications during all stages of pregnancy and the puerperium may arise suddenly. Preeclampsia is a common obstetrical condition for which magnesium sulfate is used for seizure prophylaxis. However, magnesium sulfate is strongly contraindicated in MG as it impairs already slowed nerve-muscle connections. Similarly, many first-line antihypertensive medications, including calcium channels blockers and β-blockers, may lead to MG exacerbation. This case describes the effective obstetrical management of a patient with MG who developed severe preeclampsia. The effective use of levetiracetam and various antihypertensive medications including intravenous labetalol is described. A review of the ten reported cases of MG complicated by preeclampsia is examined to aggregate observations of clinical care, with focus on delivery methods, anticonvulsants, and antihypertensive medications.


A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor.
Although pancreatic neuroendocrine tumors generally have a far better prognosis relative to pancreatic cancer, the varied manifestations lead to treatment-related challenges. Everolimus therapy is generally recommended for patients with advanced pancreatic neuroendocrine tumors; however, its efficacy in a neoadjuvant setting remains unclear. Here we present a case of a giant pancreatic neuroendocrine tumor with a portal tumor thrombus that became resectable after everolimus therapy. A 62-year-old woman was admitted to our hospital for surgical resection of a giant pancreatic neuroendocrine tumor in the left upper abdomen. Unfortunately, she was ineligible for surgery because the tumor had extended near the hepatic hilus in the portal vein, and she was administered everolimus (10 mg/day). After 2 years of this therapy, the extent of portal vein involvement had decreased, despite the lack of significant changes in the tumor size, and the hepatic hilus became free of disease. She was subsequently referred to us for resection via distal pancreatectomy with portal vein reconstruction because the tumor had begun to grow slowly. Pathological review identified a grade 2 neuroendocrine tumor with no lymph node metastasis. The patient's postoperative course was uneventful, and she has remained recurrence-free for 27 months, despite a lack of additional treatment. Our experience suggests that everolimus could be useful for neoadjuvant therapy in cases of locally advanced pancreatic neuroendocrine tumor.


Evaluating risk factors for Clostridium difficile infection in adult and pediatric hematopoietic cell transplant recipients.
Although hematopoietic cell transplant (HCT) recipients are routinely exposed to classic risk factors for Clostridium difficile infection (CDI), few studies have assessed CDI risk in these high-risk patients, and data are especially lacking for pediatric HCT recipients. We aimed to determine incidence and risk factors for CDI in adult and pediatric allogeneic HCT recipients. CDI was defined as having diarrhea that tested positive for C. difficile via PCR, cytotoxin assay, or dual enzyme immunoassays. We included all patients who received an allogeneic HCT from 2008 to 2012 at the Fred Hutchinson Cancer Research Center; those <1 year old or with CDI within 8 weeks pre-HCT were excluded. Patients were categorized by transplanting hospital ("adult" or "pediatric") and followed for 100 days post-HCT. Of 1182 HCT recipients, CDI was diagnosed in 17 % (33/192) of pediatric recipients for an incidence of 20 per 10,000 patient-days, and 11 % (107/990) of adult recipients for an incidence of 12 per 10,000. Pediatric recipients were diagnosed a median of 51 days (interquartile range [IQR]: 5, 72) after HCT and adults at 16 days (IQR = 5, 49). Compared with calendar year 2008, pediatric recipients transplanted in 2012 were at increased risk for CDI (hazard ratio [HR] = 3.99, p =.02). Myeloablative conditioning increased CDI risk in adult recipients (HR = 1.81, p =.005). Pediatric and adult allogeneic recipients are at high risk of CDI post-HCT, particularly adult recipients of myeloablative conditioning. Differences in CDI incidence between children and adults may have resulted from exposure differences related to age; therefore, separately evaluating these groups should be considered in future CDI studies.


Opportunities Missed: Cervix Cancer Screening Failures in Women Aged 65 and Older.
This study aimed to determine the screening history and associated outcomes of women diagnosed with cervical cancer after age 65. All patients from 2012 to 2021 diagnosed with squamous, adenocarcinoma, neuroendocrine, or adenosquamous cervical cancer after age 65 in a single managed care organization (MCO) were included in this retrospective cohort study. Demographic, medical, screening, pathologic, follow-up, and treatment data were extracted. Statistical analysis was done using chi-square test and logistic regression. Cancer-specific survival was estimated using the Kaplan-Meier method. Of 2,175 patients screened, 209 met inclusion criteria. Only 26.3% of patients had appropriate cervical cancer screening and 41% of patients died of their disease. Managed care organization membership duration of more than 5 years positively correlated with proper cervical cancer screening ( p < .001); however, 64% of the long-term members still did not meet criteria to end screening at age 65, with 42.6% of these patients having more than 25 physician visit opportunities to address screening. Increased physician visits correlated with earlier stage at diagnosis of cervical cancer ( p = .012). Median cancer-specific survival was significantly better in properly screened patients at 68 vs 30 months, respectively ( p = .03). Most patients diagnosed with cervical cancer after age 65 did not have adequate previous screening, including those who were MCO members for more than 5 years. There were many missed opportunities for screening, despite multiple provider touchpoints. The authors' data suggest that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.


Bidirectional band-switchable nano-film absorber from narrowband to broadband.
We propose a switchable perfect absorber with broadband and narrowband absorption based on alternating dielectric and metal nano-film structures in this paper. The lithography-free pattern is equipped with polarization insensitivity, good ductility and manufacturability, which has great significance in practical device development and applications. The quasi-complete selective absorption of incident light can be originated from asymmetric Fabry-Perot resonance, which combines the destructive interference in dielectric layers with inherent absorption in metal layers. When the light incidents on the surface covered with ultra-thin metal film of this structure, it acts as a narrowband absorber with over 99.90% absorption at 771 nm wavelength and a full wave at half maximum of 20 nm. When the light incidents on other surfaces covered with anti-reflective dielectric film, it achieves broadband perfect absorption with an average absorption exceeding 96.02% in a 500-1450 nm wavelength range. The absorption spectrum of oblique incidence shows that the broadband absorption behaves big angle range tolerance while the narrowband absorption exhibits angular dependence. The band-switchable performance of this absorber makes it valuable for energy harvesting/re-radiation applications in solar thermal photovoltaic systems.


Experimental evidence of the tonic vibration reflex during whole-body vibration of the loaded and unloaded leg.
Increased muscle activation during whole-body vibration (WBV) is mainly ascribed to a complex spinal and supraspinal neurophysiological mechanism termed the tonic vibration reflex (TVR). However, TVR has not been experimentally demonstrated during low-frequency WBV, therefore this investigation aimed to determine the expression of TVR during WBV. Whilst seated, eight healthy males were exposed to either vertical WBV applied to the leg via the plantar-surface of the foot, or Achilles tendon vibration (ATV) at 25 Hz and 50 Hz for 70s. Ankle plantar-flexion force, tri-axial accelerations at the shank and vibration source, and surface EMG activity of m. soleus (SOL) and m. tibialis anterior (TA) were recorded from the unloaded and passively loaded leg to simulate body mass supported during standing. Plantar flexion force was similarly augmented by WBV and ATV and increased over time in a load- and frequency dependent fashion. SOL and TA EMG amplitudes increased over time in all conditions independently of vibration mode. 50 Hz WBV and ATV resulted in greater muscle activation than 25 Hz in SOL when the shank was loaded and in TA when the shank was unloaded despite the greater transmission of vertical acceleration from source to shank with 25 Hz and WBV, especially during loading. Low-amplitude WBV of the unloaded and passively loaded leg produced slow tonic muscle contraction and plantar-flexion force increase of similar magnitudes to those induced by Achilles tendon vibration at the same frequencies. This study provides the first experimental evidence supporting the TVR as a plausible mechanism underlying the neuromuscular response to whole-body vibration.


Gray matter alterations in tremor-dominant Parkinson's disease after MRgFUS thalamotomy are correlated with tremor improvement: a pilot study.
Regional differences in gray matter volume (GMV) have been reported to be a reliable marker for diagnosing Parkinson's disease (PD). This study aimed to explore the clinical value of GMV to assess magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment for tremor-dominant PD (TDPD). Nine TDPD patients with MRgFUS thalamotomy were recruited for structural magnetic resonance image (MRI) scanning and clinical score evaluation. GMV was calculated. To investigate changes after treatment, voxel- and region of interest (ROI)-wise GMV analyses were performed. Then, GMV with significant differences was extracted from patients to investigate its dynamic alterations by one-way repeated-measures analysis of variance (ANOVA). The nonparametric Spearman rank correlation analysis was used to evaluate the relationship between GMV alterations and tremor improvement after thalamotomy. Tremors were significantly relieved after MRgFUS thalamotomy in nine patients (P<0.05). The treated hand tremor scores improved 74.82% on average in patients from pre-operation to 12 months post-operation. Voxel-wise analysis at the cluster level showed a significant decrease in GMV in the left middle occipital gyrus (MOG) [t=11.81, voxel-level P<0.001, cluster-level Pfamily-wise error (FWE) <0.05] and an increase in GMV in the left precentral gyrus (PreCG) (t=7.99, voxel-level P<0.001, cluster-level PFWE <0.05) in TDPD patients from preoperative to 12 months post-operation, which was significantly correlated with tremor scores (rho =0.346-0.439, P<0.05). ROI-wise analysis showed that GMV related to MRgFUS thalamotomy was associated with long-term structural alterations (P<0.05 with Bonferroni correction), including specific basal ganglia and related nuclei and cerebellum subregions. GMV can be used to reflect tremor improvement after MRgFUS thalamotomy and be helpful to better understand the distant effect of MRgFUS thalamotomy and the involvement of GMV in tremor control in TDPD. ClinicalTrials.gov identifier: NCT04570046.


Does the duration of childhood starvation affect life at age 45 or older in China? The mediating role of socioeconomic and health statuses.
This study investigated the impact of the duration of childhood starvation experience on life satisfaction among Chinese people and examined whether and how socioeconomic and health statuses mediated this association. Data were derived from the China Health and Retirement Longitudinal Study, a nationwide social survey project that was conducted among Chinese individuals aged 45 or older in 2014. The results show that the duration of childhood starvation experience was significantly negatively associated with life satisfaction, and socioeconomic and health statuses mediated this relationship. The findings suggested that more interventions should be conducted among people who have experienced childhood starvation.


Mechanism of action of Moloney murine leukemia virus RNase H III.
The mechanism of action of Moloney murine leukemia virus RNase H III was studied, utilizing the model substrate (A)n. (dT)n and polyacrylamide gel electrophoresis to assay enzyme activity. Examination by electrophoresis on 15% polyacrylamide gels in 7 M urea and on DEAE-cellulose paper in 7 M urea revealed that, early in a reaction with [3H](A)n. (dT)n as substrate, RNase H III generated products ranging in length from 80 to 90 nucleotides to less than 10 nucleotides and that after extended incubation the limit digest products generated were 3 to 15 nucleotides long. Product oligomers were of the following configuration: [5'-P, 3'-OH](A)n. RNase H III was shown to be an exonuclease requiring free ends in its substrate for activity by the inability to degrade RNA inserted in Escherichia coli ColE1 plasmid DNA. The enzyme was capable of attacking RNA in RNA-DNA hybrids in the 5' to 3' and 3' to 5' directions as demonstrated by the use of [3H, 5'-32P](A)600. (dT)n and cellulose-[3H](A)n. (dT)n. Rnase H III was random in its mode of action because addition of excess unlabeled (A)n. (dT)n to an ongoing reaction with [3H](A)n. (dT)n as substrate resulted in immediate inhibition of enzyme activity.


Versatile platform employing desorption electrospray ionization mass spectrometry for high-throughput analysis.
A simple and easy-to-build high-throughput analysis system was constructed. The system consisted of three major components: (1) a multichannel device with 16 parallel capillaries, (2) a desorption electrospray ionization (DESI) source, and (3) a linear ion trap mass spectrometer. When analyses were performed, the multichannel device was moved horizontally on a translation stage controlled by a step motor. Our design expands the functions of DESI, in which the liquid sample in capillary was driven out by the nebulizing gas, ionized, and then transferred to a mass spectrometer. To assess the high-throughput performance of the system, 5 mg/L 1,3-diethyl-1,3-diphenylurea (DDU) solution and 10 mg/L angiotensin I solution were alternatively loaded into the reservoirs and capillaries in the multichannel device. Results indicated that analyses of the all the samples in 16 capillaries were completed within 1.6 min, which means a throughput of 600 samples/h. Reactive DESI experiment was also successfully performed with this system to show the feasibility of online derivatization. The relative standard deviations for a single capillary and five identical capillaries were 7.6 (n = 16) and 12.3%, respectively. Linear relative abundance response was achieved for DDU (r = 0.9971).


Empathic accuracy: age differences from adolescence into middle adulthood.
This study investigated age differences in empathic accuracy, the ability to correctly perceive others' emotions, in a sample of 151 boys and men from three age groups: adolescents (Mage = 16 years, SD = 1.04), young adults (Mage = 29 years, SD = 2.78), and middle-aged adults (Mage = 50 years, SD = 3.07). All participants viewed nine newly developed film clips, each depicting a boy or a man reliving one of three emotions (anger, sadness, or happiness), while talking about an autobiographical memory. Adolescents and middle-aged men were less accurate than young men, and these age differences were associated with parallel age differences in fluid-mechanical abilities. In addition, age differences in vocabulary, one indicator of crystallized-pragmatic intelligence, were associated with age differences in empathic accuracy in adolescent and young, but not middle-aged, men. Within the limitations of cross-sectional data, this study provides evidence for the idea that empathic accuracy is an effortful task that requires cognitive resources and, thus, may show a normative increase until young adulthood followed by periods of stability and decline in subsequent decades.


Mental health sequelae of bullying: a review and case report.
This paper is a review of the effects of bullying on children and adolescents. We begin with a case report of a young male who presented at a children's hospital emergency room after being subjected to months of bullying. We then proceed to a review of relevant literature, and focus on a definition of bullying, the incidence of this problem, and the characteristics of bullies, victims and those who both bully and are bullied. The consequences of this behaviour, both for the perpetrator and victim, are also examined. We note that all individuals who participate in bullying, whether as perpetrators, victims, or those who have been both the perpetrators and the targets of this particular form of aggression, have in some way been psychologically affected by such experiences. It is hoped that the significance of bullying behaviour, and its psychological cost on the psychological well-being of the children and adolescents involved with bullying, will be a central theme of this review.


Pneumatic Rupture of Rectosigmoid; a Case Report.
Pneumatic rectosigmoid rapture is usually occurred following the inappropriate fun by direct entering a high volume of the air through the pneumatic device to the anus. Such an event was reported for the first time in 1904 by Stone. Diagnosis and treatment of such injuries are often delayed because of some social limitations and preventing the patient form explaining the event. Colon sigmoid rupture and pneumoperitoneum is one of the most dangerous and life treating complications of entering a high volume of the air to the rectum in a short time. There are only a few reports regarding the similar cases. Here, a case of pneumatic rectosigmoid rapture was reported in a 53 year-old male following an inappropriate fun.


A case of a chlorine inhalation injury in an Ebola treatment unit.
We present a 26-year-old male British military nurse, deployed to Sierra Leone to treat patients with Ebola virus disease at the military-run Kerry Town Ebola Treatment Unit. Following exposure to chlorine gas during routine maintenance procedures, the patient had an episode of respiratory distress and briefly lost consciousness after exiting the facility. Diagnoses of reactive airways disease, secondary to the chlorine exposure and a hypocapnic syncopal episode were made. The patient was resuscitated with minimal intervention and complete recovery occurred in less than 1 week. This case highlights the issues of using high-strength chlorine solution to disinfect the red zone. Although this patient had a good outcome, this was fortunate. Ensuring Ebola treatment centres are optimally designed and that appropriate management systems are formulated with extraction scenarios rehearsed are important to mitigate the chlorine-associated risk.


Effects of continuous high-volume hemofiltration on experimental severe acute pancreatitis in pigs.
To compare the effects of different doses of hemofiltration on severe acute pancreatitis (SAP) in pigs. The animal model of SAP was produced by intraductal injection of sodium taurocholate and trypsin. Animals in group 1 served as SAP control. Animals in group 2 received (20 mL/kg per hour) continuous low-volume hemofiltration (LVHF), and animals in group 3 received (100 mL/kg per hour) continuous high-volume hemofiltration (HVHF) immediately after the induction of SAP. After the instrumentation of the animals by arterial and Swan-Ganz catheters, hemodynamic indexes were monitored intermittently at different times. The rectal temperature and the concentration of amylase and cytokines in serum were measured at the same time. The survival time of HVHF group was significantly prolonged (P < 0.01). The initial elevation of body temperature and the hypothermia in the late course of experiments were significantly ameliorated by HVHF (P < 0.01). Six hours after the induction of pancreatitis, the urine output of animals in HVHF group was obviously higher than that in control group (P < 0.05), which stayed behind 36 hours later (P < 0.05). The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by HVHF (P < 0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in CI, an attenuated decrease in systemic vascular resistance index. Plasma amylases in the HVHF group were significantly lower than those in control and LVHF groups (P < 0.01). The serum concentrations of cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 6, and IL-10 all decreased significantly in treatment groups (P < 0.01), and those of HVHF group were less significant than the HVHF group (P < 0.01). The HVHF was associated with a better hemodynamic profile, a less hyperkinetic state, and more prolonged survival than that of LVHF, which may result from the HVHF that can remove the inflammatory cytokines more efficiently.


Ethanol enhancement of Pavlovian conditioning: comparison with instrumental conditioning.
Yoked pairs of rabbits received conditioning and extinction of eyeblink and heart rate responses using aversive Pavlovian versus instrumental avoidance contingencies. A low dose of ethanol (375 mg/kg) increased the amplitude of conditioned eyeblink responses during training and during subsequent extinction following either ethanol or water; this effect was more pronounced in the Pavlovian than the instrumental contingency groups. Ethanol treatment did not affect the cardiac component of the Orienting Reflex to novel tones or heart rate conditioned responses to tone signals, but did bias heart rate responses to tone-shock stimulus pairs in a parasympathetic direction; this effect occurred in both contingency groups but appeared to involve associative factors. These results support the conclusion that mild ethanol intoxication enhances the acquisition of Pavlovian conditioned reflexes, and impairs the ability to modify these responses when stimulus contingencies later change.


[Cholesterol absorption as a target for the treatment of hypercholesterolemia].
Hypercholesterolemia is a major risk factor for atherosclerosis. HMG-CoA Reductase inhibitors (statins), which block hepatic synthesis of cholesterol, are the mainstay of therapy of hypercholesterolemia. Recent trials have demonstrated the importance of maintaining very low LDL-cholesterol levels in high-risk patients. Such low levels are sometimes hard to reach with statin monotherapy. Another source of cholesterol is intestinal absorption of dietary cholesterol and bile salts. Recent studies have elucidated the mechanism of intestinal cholesterol absorption. Ezetimibe, a specific inhibitor of cholesterol absorption can be used as an add-on therapy to statins in order to achieve treatment goals.


Serum FGF21 and RBP4 levels in patients with chronic hepatitis C.
Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (β = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (β = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.


Primary chylopericardium associated with allergic alveolitis.
A 42-year-old woman with extrinsic allergic alveolitis and worsening dyspnea was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid containing microscopic fat droplets. The pericardial effusion resolved with prednisone therapy.


Dual array 3D electron cyclotron emission imaging at ASDEX Upgrade.
In a major upgrade, the (2D) electron cyclotron emission imaging diagnostic (ECEI) at ASDEX Upgrade has been equipped with a second detector array, observing a different toroidal position in the plasma, to enable quasi-3D measurements of the electron temperature. The new system will measure a total of 288 channels, in two 2D arrays, toroidally separated by 40 cm. The two detector arrays observe the plasma through the same vacuum window, both under a slight toroidal angle. The majority of the field lines are observed by both arrays simultaneously, thereby enabling a direct measurement of the 3D properties of plasma instabilities like edge localized mode filaments.


Nursing Professional Identity: A Cross-Sectional Study.
Becoming a good nurse is a mandatory goal for each nurse and a daily challenge. Nurses have the responsibility to maintain the highest level of professional integrity and quality not only to protect patients and their families but also to positively influence nursing students. In fact, students learn how to become good nurses if they really experience that from all nurses they meet during their training. It could be useful to take a "general picture" of nurses who work every day into our hospitals. To evaluate the level of nursing professional identity. A cross-sectional study was designed. An anonymous structured questionnaire was administered to nurses in a hospital Rome. 334 nurses participated and they were mainly female (80%); mean age: 37.11ys (SD 8.49); 15.87% had health professionals in family, and nursing profession was the first choice for the 72.16%; 93.71% had family support. In nursing profession, empathy and both human and technical requirements were important for more than 94.91%. 84.73% would repeat the nursing choice, and 79.64% would recommend that. Only 64.97% was satisfied about their profession. Nursing profession is a controversial profession, with motived and passionate professionals but still unsatisfied. Professional identity is a delicate and complex topic, and an essential part that consistently influences the personal attitude to reach the best nursing practice. Professional identity is one of the first aspects to take into account to better understand in which way nurses could influence colleagues, patients and their families, and finally nursing students during their daily practice.


A non-contact, thermal noise based method for the calibration of lateral deflection sensitivity in atomic force microscopy.
Calibration of lateral forces and displacements has been a long standing problem in lateral force microscopies. Recently, it was shown by Wagner et al. that the thermal noise spectrum of the first torsional mode may be used to calibrate the deflection sensitivity of the detector. This method is quick, non-destructive and may be performed in situ in air or liquid. Here we make a full quantitative comparison of the lateral inverse optical lever sensitivity obtained by the lateral thermal noise method and the shape independent method developed by Anderson et al. We find that the thermal method provides accurate results for a wide variety of rectangular cantilevers, provided that the geometry of the cantilever is suitable for torsional stiffness calibration by the torsional Sader method, in-plane bending of the cantilever may be eliminated or accounted for and that any scaling of the lateral deflection signal between the measurement of the lateral thermal noise and the measurement of the lateral deflection is eliminated or corrected for. We also demonstrate that the thermal method may be used to characterize the linearity of the detector signal as a function of position, and find a deviation of less than 8% for the instrument used.


Rapid, Sensitive, Label-Free Electrical Detection of SARS-CoV-2 in Nasal Swab Samples.
Rapid diagnosis of coronavirus disease 2019 (COVID-19) is key for the long-term control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amid renewed threats of mutated SARS-CoV-2 around the world. Here, we report on an electrical label-free detection of SARS-CoV-2 in nasopharyngeal swab samples directly collected from outpatients or in saliva-relevant conditions by using a remote floating-gate field-effect transistor (RFGFET) with a 2-dimensional reduced graphene oxide (rGO) sensing membrane. RFGFET sensors demonstrate rapid detection (<5 min), a 90.6% accuracy from 8 nasal swab samples measured by 4 different devices for each sample, and a coefficient of variation (CV) < 6%. Also, RFGFET sensors display a limit of detection (LOD) of pseudo-SARS-CoV-2 that is 10 000-fold lower than enzyme-linked immunosorbent assays, with a comparable LOD to that of reverse transcription-polymerase chain reaction (RT-PCR) for patient samples. To achieve this, comprehensive systematic studies were performed regarding interactions between SARS-CoV-2 and spike proteins, neutralizing antibodies, and angiotensin-converting enzyme 2, as either a biomarker (detection target) or a sensing probe (receptor) functionalized on the rGO sensing membrane. Taken together, this work may have an immense effect on positioning FET bioelectronics for rapid SARS-CoV-2 diagnostics.


Preventing newborn infection with maternal immunization.
Group B streptococcal disease is a common cause of bacterial sepsis in newborns and is often fatal. To protect these babies, a vaccination program must target pregnant women for immunization so that the resulting antibodies can be passively delivered from the mother to the fetus. Scientists met in Siena, Italy, to discuss potential approaches to maternal immunization for the prevention of perinatal group B streptococcal disease.


Baculovirus expression of the fusion protein gene of bovine respiratory syncytial virus and utility of the recombinant protein in a diagnostic enzyme immunoassay.
The fusion (F) protein of bovine respiratory syncytial virus (BRSV) was expressed by using a baculovirus vector. Antigenicity was tested by immunofluorescence analysis with F-specific monoclonal and polyclonal antibodies. Antibodies to recombinant F protein raised in a rabbit neutralized BRSV and human respiratory syncytial virus infectivity when tested in a plaque reduction assay. The recombinant F protein was evaluated as a source of antigen in an enzyme-linked immunosorbent assay (ELISA), and this ELISA was compared with the virus neutralization (VN) test for detecting BRSV antibodies in 10 consecutive serum samples from four calves vaccinated with a live modified BRSV vaccine and from two nonvaccinated control calves. The ELISA with the baculovirus-expressed F protein as an antigen compared favorably with the VN test and is a rapid, sensitive, and specific method for detecting serum antibodies to BRSV.


Valproic acid in the treatment of epilepsy during the pediatric age.
We studied 85 pediatric patients with different types of epilepsy treated with valproic acid. The clinical and EEG follow-up were performed up to 10 months. Our EEG-clinical observations in this study show that this group of epilepsies during the pediatric age are extremely sensitive to valproic acid with minimal and tolerable side effects. Within a brief period of time an effective response was obtained in the case of epilepsy with myoclonicastatic seizures juvenile myoclonic epilepsy (impulsive petit mal), classical absence and photosensitive epilepsy.


The complete mitochondrial genome of western Mediterranean mouse, Mus spretus (Rodentia: Muridae).
The western Mediterranean mouse (Mus spretus) is a wide-spread and well-studied small mammal species in Europe. In this study, we report the complete mitochondrial genome sequence of this species for the first time. Data analysis shows that this mitogenome is entirely 16,286 bp in length and has a conservative genomic organization and gene order as most other mice. The overall nucleotide base composition is 34.1% of A, 28.6% of T, 24.6% C, and 12.7% G, with a strong A + T bias of 62.7%. All the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes, which are distributed on the L-strand. Totally 13 protein-coding genes initiate with ATN/GTG start codon and terminate with the typical stop codon (TAA/TAG) or a single T (T- -). Most of the transfer RNA genes could fold into the typical clover-leaf structure except for tRNA(Leu) and tRNA(Ser), whose dihydrouridine (DHU) arm are lost. The complete mitochondrial genome sequence reported here will be useful for population genetic and phylogenetic studies in mice.


Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow.
Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage. EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score. Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke.


Retrospective Evaluation of Poisoning Cases Followed Up in a Pediatric Intensive Care Unit-A 12-Year Experience in a Single Center.
Poisonings constitute an important part of preventable morbidity and mortality in pediatric intensive care units (PICUs) and hospitalizations. However, information on poisoning requiring intensive care is limited. This study aimed epidemiological evaluation of poisoning cases treated in the PICU in a single center. The records of 504 patients admitted to the PICU due to acute poisoning between 2010 and 2022 were retrospectively reviewed. Data were evaluated using descriptive methods and the χ 2 test, and statistical differences with P value <0.05 were considered significant. The age range of the patients ranged from 1 month to 216 months (18 years), and the rate of girls was 53.2% (n = 268), whereas the rate of boys was 46.8% (n = 236). The mean age was 4.4 ± 4.3 years for boys, 6.7 ± 5.8 years for girls, and 5.6 ± 5.3 years for all patients. It was determined that 79.6% of the cases were poisoned by accident and 20.4% by suicide. A total of 76.7% of the patients who were poisoned for suicide were girls and 23.3% were boys. The mean age of these patients was 14.3 ± 3.0 years. On the other hand, 47.1% of the children who were accidentally poisoned were girls and 52.9% were boys, and the mean age of these children was 3.4 ± 2.9 years. Although 79.9% of poisonings occurred at home, the causative agent was oral poisoning in 97.4% of the cases. Approximately two thirds (69.2%) of the cases were drug-related, whereas 30.8% were related to nondrug substances. In drug-related poisonings, central nervous system drugs (35.8%) were the most common agent, followed by analgesic/antipyretic (20.9%) agents, whereas among the nonpharmaceutical factors, insecticides (agricultural pesticides, rat poison, pesticides, etc) were the most common, followed by poisonous herbs (beetleweed, widow's weed, cannabis, etc). The mean admission time of the patients to the hospital was 6.3 ± 8.4 hours, and the mean length of stay in the intensive care unit was 1.6 ± 1.3 days. In the 12 years of our study, only 3 patients died due to poisoning, and our mortality rate was 0.5%. Four patients (0.7%) were referred to the Alcohol and Drug Addicts Treatment and Research Center. In this study, in which we retrospectively analyzed the profiles of poisoning cases hospitalized in the PICU for 12 years, we determined that poisonous weeds were the major factor in accidental poisonings, and suicidal poisonings were above the expected rates even at the young age group such as 8-12 years old. These results show the importance of determining the poisoning profile of the health care service area.


Limits of quintessence.
We present evidence that the simplest particle-physics scalar-field models of dynamical dark energy can be separated into distinct behaviors based on the acceleration or deceleration of the field as it evolves down its potential towards a zero minimum. We show that these models occupy narrow regions in the phase plane of w and w', the dark energy equation of state and its time derivative in units of the Hubble time. Restricting an energy scale of the dark energy microphysics limits how closely a scalar field can resemble a cosmological constant. These results, indicating a desired measurement resolution of order sigma(w') approximately = (1+w), define firm targets for observational tests of the physics of dark energy.


Fibrinolysis in the rat after short-term aspirin therapy.
Fibrinolytic parameters were compared in blood taken from rats treated with aspirin (10 and 40 mg/kg) or saline solution. Plasma euglobulin fractions prepared from animals treated with the higher dose of aspirin caused increased zones of lysis on plasminogen-rich fibrin plates. Even greater lytic activity was detected in blood from all aspirin-treated rats when euglobulin fractions were augmented with sodium flufenamate and dextran sulfate. The inhibitor index was significantly reduced when calculated for rats treated with the larger dose of drug. Dilute blood clot lysis times for this group were consistently prolonged, most likely reflecting impaired platelet function. Platelet counts, hematocrits, and bleeding times did not differ from controls. Prothrombin times, activated partial thromboplastin times, and plasma clot times were all prolonged, reflecting the sensitivity of the vitamin K-dependent factors to aspirin.


Recruitment of community-dwelling older adults for nursing research: a challenging process.
In the face of changing demographics, the need for gerontological nursing research has become central to the development of relevant health and social policies and resources for older adults. The recruitment of community-dwelling older adults presents multiple challenges for the nurse researcher wishing to conduct meaningful research. A common concern cited in the literature is the recruitment of sufficient numbers of older participants. The recruitment of persons 65 years of age and older is influenced by factors such as gender and study design as well as physical, social, psychological, and age-related changes. This paper describes these factors, as well as effective strategies for recruiting older adults, the authors' conceptualization of a 3-phase recruitment process, and key points for the nurse researcher to consider when recruiting subjects.


Small Gut Volvulus, A Rare Twist, In The Setting Of An Even Rarer Entity; Multiple Giant Jejuno Ileal Diverticula.
Small gut volvulus with multiple Jejuno-ileal diverticulosis is an unusual pathology of the small intestine with a scarce number of cases reported so far. It usually goes unnoticed because it is often asymptomatic but complications like diverticulitis, perforation, bleeding or intestinal obstruction can occur in 10-30% of the cases. Mechanical obstruction, if it occurs, can be caused by adhesions or stenosis due to diverticulitis, intussusception at the site of the diverticulum and volvulus of the segment containing the diverticula. Acute volvulus of the small bowel is a serious abdominal emergency that poses a difficulty in diagnosis and delayed operative intervention can lead to dire consequences. We herein report the case of a 42-yearold man presented at the emergency department with acute abdominal pain, absolute constipation and vomiting. Preoperative investigations followed by laparotomy revealed small gut volvulus and multiple giant jejunal and ileal diverticula.


Identification of an ovulation rate QTL in cattle on BTA14 using selective DNA pooling and interval mapping.
Increased twinning incidence in beef cattle has the potential to improve production efficiency. However, phenotypic selection for twinning rate is difficult because of the trait's low heritability and the long time interval necessary to collect phenotypic records. Therefore, this trait and the correlated trait of ovulation rate are ideal candidates for marker-assisted selection. The objective of this study was to complete a genome-wide search for ovulation rate quantitative trait loci (QTL) in two related sire families. The families (paternal halfsib sires 839802 and 839803) were from a population of cattle selected for ovulation rate at the USDA Meat Animal Research Center, Clay Center, Nebraska. Putative ovulation rate QTL have previously been identified in the 839802 family on chromosomes 7 and 19; however, marker coverage in the original scan was not complete. This study fills the gaps in marker coverage of the earlier study by adding approximately 60 informative microsatellites to each sire family. Each family was genotyped using selective DNA pooling. Sons and daughters were included in either the high or low pool based on their estimated breeding value deviations from the mid-parent average (EBVMD) for ovulation rate. Approximately 40% (839802) and 26% (839803) of available progeny comprised the high and low pools combined. Pooled typing revealed possible associations (nominal P < 0.05) between ovulation rate and marker genotype for 11 and 15 microsatellites in the 839802 and 839803 families, respectively. Subsequent interval mapping strengthened support for the presence of an ovulation rate QTL on BTA14 (chromosome-wise P < 0.02).


Functions of aldehyde reductases from Saccharomyces cerevisiae in detoxification of aldehyde inhibitors and their biotechnological applications.
Bioconversion of lignocellulosic biomass to high-value bioproducts by fermentative microorganisms has drawn extensive attentions worldwide. Lignocellulosic biomass cannot be efficiently utilized by microorganisms, such as Saccharomyces cerevisiae, but has to be pretreated prior to fermentation. Aldehyde compounds, as the by-products generated in the pretreatment process of lignocellulosic biomass, are considered as the most important toxic inhibitors to S. cerevisiae cells for their growth and fermentation. Aldehyde group in the aldehyde inhibitors, including furan aldehydes, aliphatic aldehydes, and phenolic aldehydes, is identified as the toxic factor. It has been demonstrated that S. cerevisiae has the ability to in situ detoxify aldehydes to their corresponding less or non-toxic alcohols. This reductive reaction is catalyzed by the NAD(P)H-dependent aldehyde reductases. In recent years, detoxification of aldehyde inhibitors by S. cerevisiae has been extensively studied and a huge progress has been made. This mini-review summarizes the classifications and structural features of the characterized aldehyde reductases from S. cerevisiae, their catalytic abilities to exogenous and endogenous aldehydes and effects of metal ions, chemical protective additives, and salts on enzyme activities, subcellular localization of the aldehyde reductases and their possible roles in protection of the subcellular organelles, and transcriptional regulation of the aldehyde reductase genes by the key stress-response transcription factors. Cofactor preference of the aldehyde reductases and their molecular mechanisms and efficient supply pathways of cofactors, as well as biotechnological applications of the aldehyde reductases in the detoxification of aldehyde inhibitors derived from pretreatment of lignocellulosic biomass, are also included or supplemented in this mini-review.


A quantitative method for screening and identifying molecular targets for nanomedicine.
Identifying a molecular target is essential for tumor-targeted nanomedicine. Current cancer nanomedicines commonly suffer from poor tumor specificity, "off-target" toxicity, and limited clinical efficacy. Here, we report a method to screen and identify new molecular targets for tumor-targeted nanomedicine based on a quantitative analysis. In our proof-of-principle study, we used comparative flow cytometric screening to identify ICAM-1 as a potential target for metastatic melanoma (MM). We further evaluated ICAM-1 as a MM targeting moiety by characterizing its (1) tumor specificity, (2) expression level, (3) cellular internalization, (4) therapeutic function, and (5) potential clinical impact. Quantitation of ICAM-1 protein expression on cells and validation by immunohistochemistry on human tissue specimens justified the synthesis of antibody-functionalized drug delivery vehicles, which were benchmarked against appropriate controls. We engineered ICAM-1 antibody conjugated, doxorubicin encapsulating immunoliposomes (ICAM-Dox-LPs) to selectively recognize and deliver doxorubicin to MM cells and simultaneously neutralize ICAM-1 signaling via an antibody blockade, demonstrating significant and simultaneous inhibitory effects on MM cell proliferation and migration. This paper describes a novel, quantitative metric system that identifies and evaluates new cancer targets for tumor-targeting nanomedicine.


Hyperreactio luteinalis encountered during caesarean delivery of an uncomplicated spontaneous singleton pregnancy.
We report a rare case of hyperreactio luteinalis presenting as an incidental finding during caesarean section in an uncomplicated spontaneous singleton pregnancy. Caesarean section was performed due to failure to progress in labour, and delivered a healthy male neonate. The mother's analytical tests revealed a hyperandrogenic state without any other relevant alterations. Ovarian volume and testosterone serum concentration normalised in 2 months. The expectant management of this case permitted conservation of both ovaries in a young woman without adding morbidity.


Epidemiological Patterns of Common Cancers in Costa Rica: An Overview up to 2020.
The increasing cancer incidence and mortality rates in Costa Rica have become a public health concern, with prostate, breast, and colorectal cancers being the most prevalent. This study aimed to analyze the trends in cancer incidence and mortality rates by tumor type, sex, age group, and geographic region using data from the Costa Rican National Cancer Registry. In this retrospective study, we analyzed cancer incidence and mortality anonymized data from the Costa Rican National Cancer Registry between 2010 and 2020. The study included data on cancer cases diagnosed and deaths attributable to cancer within the population. Our findings revealed variations in cancer incidence and mortality rates based on geographic region, age group, and tumor type. Cancer was most predominant in the province of San Jose, followed by Alajuela, Heredia, Cartago, Guanacaste, and Puntarenas. Breast cancer, colorectal cancer, and prostate cancer were the leading causes of cancer in both sexes. Mortality rates due to gastric cancer and prostate cancer were highest among men, while breast cancer was the leading cause of cancer mortality among women. The results of this study underscore the need for targeted prevention and screening programs, improved access to treatment for patients living in rural areas, and a comprehensive cancer control program in Costa Rica. By implementing evidence-based interventions, such as tobacco control programs, cancer screening initiatives, and equitable access to cancer treatment, the cancer burden in Costa Rica can be mitigated, ultimately improving the overall health of the population.


High-Frequency Hearing Loss Is Associated With Anxiety and Brain Structural Plasticity in Older Adults.
Age-related hearing loss (ARHL) is a kind of symmetrical and slow sensorineural hearing loss, which is a common condition in older adults. The characteristic of ARHL is hearing loss beginning in the high-frequency region and spreading toward low-frequency with age. Previous studies have linked it to anxiety, suggesting that brain structure may be involved in compensatory plasticity after partial hearing deprivation. However, the neural mechanisms of underlying ARHL-related anxiety remain unclear. The purpose of this cross-sectional study was to explore the interactions among high-frequency hearing loss and anxiety as well as brain structure in older adults. Sixty-seven ARHL patients and 68 normal hearing (NH) controls participated in this study, and the inclusion criterion of ARHL group was four-frequency (0.5, 1, 2, and 4 kHz) pure tone average (PTA) > 25 decibels hearing level of the better hearing ear. All participants performed three-dimensional T1-weighted magnetic resonance imaging (MRI), pure tone audiometry tests, anxiety and depression scales. Our results found gray matter volume (GMV) decreased in 20 brain regions in the ARHL group compared with the NH group, and a positive correlation existed between high-frequency pure tone audiometry (H-PT) and anxiety scores in the ARHL group. Among 20 brain regions, we also found the GMVs of the middle cingulate cortex (MCC), and the hippocampal/parahippocampal (H-P) regions were associated with H-PT and anxiety scores in all participants separately. However, the depressive symptoms indicated no relationship with hearing assessment or GMVs. Our findings revealed that the crucial role of MCC and H-P in a link of anxiety and hearing loss in older adults.


Effect of Grouping, Segmentation, and Vestibular Stimulation on the Autokinetic Effect.
We report some new observations on what could be regarded as the world's simplest visual illusion-the autokinetic effect. When a single dim spot of light is viewed in a completely dark room, it moves vividly in random directions. During steady fixation, perhaps subtle eye movements cause the image to move and a failure to correct for this using eye movement command signals leads to motion perception. This is especially true because eye muscle fatigue can lead to miscalibration. However, if two dots are shown, they often move independently in different directions, which negate the eye movement theory. In addition, two lines defining a single cross sometimes uncouple and slide past each other and the fragments composing a hidden object move independently until they click in place and the whole object is perceived-implying that the illusion occurs relatively late in visual processing. Finally, the effect is modulated by vestibular stimulation; anchoring your sense of self may be a prerequisite for binding features into coherent objects.