Attitudes towards LGBTQ+ individuals among Thai medical students.
The global population of individuals with gender diversity or LGBTQ+ people is on the rise. However, negative attitudes towards LGBTQ+ individuals persist, even among healthcare professionals, creating barriers to healthcare access. These attitudes are influenced by cultural variations worldwide and necessitate investigation across diverse cultures and settings. This study aimed to evaluate the attitudes towards LGBTQ+ people and describe associated factors with being LGBTQ+ among Thai medical students. During the 2021 academic year, a survey was conducted at a medical school in Bangkok, Thailand, collecting demographic data and attitudes measured by a standardised Thai questionnaire. Descriptive statistics as well as bivariate and multivariable logistic regression analyses were used to describe characteristics and association. A total of 806 medical students participated, with a neutral attitude being the most prevalent (72.2%), followed by a positive attitude (27.2%), and a minority reporting a negative attitude (0.6%). Bivariate and multivariable logistic regression analyses revealed significant associations between positive attitudes and female sexual identity (aOR 2.02, 95%CI 1.45-2.81, p-value < 0.001), having LGBTQ+ family members (aOR 3.57, 95%CI 1.23-10.34, p-value = 0.019), having LGBTQ+ friend (aOR 1.46, 95%CI 1.02-2.11, p-value = 0.040), and coming from areas outside of Bangkok (aOR 1.41, 95%CI 1.01-1.97, p-value = 0.043). Positive attitude towards the LGBTQ+ community are essential for physicians, emphasising the need to study factors that contribute to positive attitudes in order to foster an LGBTQ+-friendly environment for both patients and medical students.


Encapsulation Systems for Antimicrobial Food Packaging Components: An Update.
Antimicrobially active packaging has emerged as an effective technology to reduce microbial growth in food products increasing both their shelf-life and microbial safety for the consumer while maintaining their quality and sensorial properties. In the last years, a great effort has been made to develop more efficient, long-lasting and eco-friendly antimicrobial materials by improving the performance of the incorporated antimicrobial substances. With this purpose, more effective antimicrobial compounds of natural origin such as bacteriocins, bacteriophages and essential oils have been preferred over synthetic ones and new encapsulation strategies such as emulsions, core-shell nanofibres, cyclodextrins and liposomes among others, have been applied in order to protect these antimicrobials from degradation or volatilization while trying to enable a more controlled release and sustained antimicrobial action. On that account, this article provides an overview of the types of antimicrobials agents used and the most recent trends on the strategies used to encapsulate the antimicrobial agents for their stable inclusion in the packaging materials. Moreover, a thorough discussion regarding the benefits of each encapsulation technology as well as their application in food products is presented.


History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL).
A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview. The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out.


Toward a just policy on healthcare rationing. Ethical principles must inform the debate concerning the distribution of services.
Perceptions of inequity and excess have given rise to a debate over whether policymakers should consider some form of rationing as a means of achieving a more just healthcare system. Three factors will be critical in determining whether the policies ultimately developed will be just and equitable. First, participants must grasp relevant facts involving the current distribution of healthcare services in the United States. Second, the debate must be based on a clear understanding of who has ultimate responsibility for making decisions regarding healthcare rationing. Finally, those committed to implementing a just approach to the issue must ensure that ethical principles relevant to policy-making are clear to everyone and affect the debate's outcome. The controversy over whether to ration healthcare services obscures the fact that healthcare is, in reality if not in policy, rationed now. A key advantage of promoting formal public policy decisions about the provision and limitation of healthcare services is that it shifts responsibility for these decisions from providers to society. Applying four classic bioethical principles to the question of rationing can also help ensure implementation of an appropriate public policy on healthcare rationing. For the debate on rationing to be meaningful, it must be conducted in a way that respects and promotes participants' autonomy. Policymakers should also observe the principle of nonmaleficence, which dictates that their policies not harm those they affect. A proper rationing policy should also fulfill the criterion of beneficence (i.e., actively promote the good of others). Last, such a policy should conform to the principle of justice by being fair and impartial.


Human spinal cord injury causes specific increases in surface expression of β integrins on leukocytes.
Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for both circulating neutrophils and monocytes. The percentage of neutrophils and monocytes expressing the selectin CD62L was unchanged in TC and SCI patients after injury compared to uninjured subjects. Concurrently, the amount of surface CD62L on neutrophils was decreased in SCI and TC subjects, and on monocytes after SCI. The percentage of neutrophils expressing α4 decreased in TC, but not in SCI, subjects. Likewise, the percentage of neutrophils and monocytes expressing CD11d decreased markedly in TC subjects, but not after SCI. In contrast, the mean surface expression of α4 and CD11d by neutrophils and monocytes increased after SCI compared with uninjured and TC subjects. The percentage of cells and surface expression of CD11b were similar in neutrophils of all three groups, whereas CD11b surface expression increased after SCI in monocytes. In summary, unlike changes found after general trauma, the proinflammatory stimulation induced by SCI increases the surface expression of adhesion molecules on circulating neutrophils and monocytes before they infiltrate the injured spinal cord and multiple organs of patients. Integrins may be excellent targets for anti-inflammatory treatment after human SCI.


XIII. Cerebral circulation and metabolism in stroke. Cerebral circulation and metabolism in stroke study group.
An understanding of the cerebral circulation is so fundamental to comprehension of the pathogenesis of stroke that cerebral blood flow and metabolism merit review in this series of reports. The authors recognize that the research described here is very technical in nature and may appear to have little practical application to clinical medicine. Nevertheless, these matters are basic to the development of precise methods for the measurement of regional cerebral blood flow in man which could be used to monitor the therapy of stroke with greater success than is possible at present.


Axotomy-induced early down-regulation of POU-IV class transcription factors Brn-3a and Brn-3b in retinal ganglion cells.
It has been proposed that neurons being exposed to proapoptotic stimuli undergo dedifferentiation, a process that can either allow for regeneration and axon regrowth or, if remaining incomplete, can force the cell to activate apoptotic pathways. A pivotal step in the differentiation program from neuronal precursor cells to differentiated, postmitotic neurons is their exit from the cell cycle. The POU domain transcription factors Brn-3b and Brn-3a, which are expressed in retinal ganglion cells (RGCs) directly after the exit of RGC precursors from the cell cycle, can be employed as RGC-specific differentiation markers to study potential dedifferentiation of RGCs after axotomy. Here, we examined mRNAand protein expression of Brn-3a and -3b in rat RGCs following axonal lesion. We observed a rapid down-regulation of Brn-3a and -3b protein expression in axotomized RGCs, clearly preceding apoptosis of RGCs. Using real-time PCR, we show that regulation of Brn-3 expression occurred at the transcriptional level. The small subset of RGCs regenerating into a peripheral nerve graft did not (re-)express Brn-3a or -b. In conclusion, we found further evidence supporting the hypothesis of a dedifferentiation process in severed mature neurons. As Brn-3b expression has been shown to be a prerequisite for developmental survival of most RGCs and Brn-3a activates transcription of anti-apoptotic genes, down-regulation of Brn-3 transcription factors might be causally involved in the secondary death of adult RGCs following axotomy.


Tetracycline and niacinamide control bullous pemphigoid but not pemphigus foliaceus when these conditions coexist.
Pemphigus and pemphigoid are different types of autoimmune bullous disease and can occur in the same patient. We report a female patient with this condition. At first, we diagnosed her with bullous pemphigoid, and we treated her with tetracycline, niacinamide and a topical steroid. Tense bullas disappeared shortly after that, but crusted erythemas mainly on her head and trunk persisted. We examined BP180 and desmoglein 1 enzyme-linked immunosorbent assays, and also histological features, which showed coexistence of bullous pemphigoid and pemphigus foliaceus concurrently. Therefore, we tried prednisolone, which could control both conditions. This case showed that tetracycline and niacinamide could control bullous pemphigoid, but could not control pemphigus foliaceus, and that prednisolone was effective for both conditions.


Feasibility and efficacy of nurse-led team management intervention for improving the self-management of type 2 diabetes patients in a Chinese community: a randomized controlled trial.
The aim of this study was to examine the feasibility and efficacy of nurse-led team management (NLTM) intervention at improving the self-management of patients with type 2 diabetes (T2D) at community settings in Changsha, Hunan, China. China has become the country with the largest number of patients with diabetes, and that number is growing, causing increasing pressure on the health care system. At present, the main diabetes management model in China is teamwork guided by general practitioners. However, the number of general practitioners is insufficient, and their work is overloaded, which leads to poor outcomes of diabetes management. Therefore, it is important to explore alternative methods of diabetes management, such as NLTM. In a randomized controlled trial, 171 T2D patients were randomized into the control or intervention arm. Participants in the control group received routine management from the community health service center, whereas the intervention group received 12 months NLTM intervention in addition to the standard care. The diabetes self-management scale, fasting blood sugar, and glycosylated hemoglobin A1c (HbA1c) were assessed at baseline and at 6 and 12 months after the start of the intervention. Baseline data were comparable between arms. Repeated-measurement analysis showed that self-management of the intervention group improved compared with the control group after the intervention (P<0.05). There were no significant differences in HbA1c at 6 months, whereas after 12 months of intervention, there was a significant difference in HbA1c between the two groups (F=10.114, P<0.05). The intervention had no significant effect on fasting blood sugar. The NLTM intervention has resulted in an impact of practical significance on T2D self-management, and was beneficial for controlling the level of HbA1c. The study has demonstrated the feasibility and efficacy of using NLTM in the management of T2D in a Chinese community.


Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery.
Cardiac preconditioning is thought to be involved in the observed decreased coronary artery reocclusion rate in patients with angina preceding myocardial infarction. We prospectively examined whether preconditioning by sevoflurane would decrease late cardiac events in patients undergoing coronary artery bypass graft (CABG) surgery. Seventy-two patients scheduled for elective CABG surgery were randomized to preconditioning by sevoflurane (10 min at 4 vol%) or placebo. For all patients, follow-up of adverse cardiac events was obtained 6 and 12 months after surgery. Transcript levels for platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31), catalase and heat shock protein 70 (Hsp70) were determined in atrial biopsies after sevoflurane preconditioning. Pharmacological preconditioning by sevoflurane reduced the incidence of late cardiac events during the first year after CABG surgery (sevoflurane 3% vs 17% in the placebo group, log-rank test, P=0.038). One patient in the sevoflurane group and three patients in the placebo group experienced new episodes of congestive heart failure and three additional patients had coronary artery reocclusion. Perioperative peak concentrations for myocardial injury markers were higher in patients with subsequent late cardiac events [NTproBNP, 9031 (4125) vs 3049 (1906) ng litre(-1), P<0.001; cTnT, 1.31 (0.88) vs 0.46 (0.29) microg litre(-1), P<0.001]. Transcript levels were reduced for PECAM-1 and increased for catalase but unchanged for Hsp70 in atrial biopsies after sevoflurane preconditioning. This prospective randomized clinical study provides evidence of a protective role for pharmacological preconditioning by sevoflurane in late cardiac events in CABG patients, which may be related to favourable transcriptional changes in pro- and antiprotective proteins.


Clinical observations and management of a severe equine herpesvirus type 1 outbreak with abortion and encephalomyelitis.
Latent equine herpesvirus type 1 (EHV-1) infection is common in horse populations worldwide and estimated to reach a prevalence nearing 90% in some areas. The virus causes acute outbreaks of disease that are characterized by abortion and sporadic cases of myeloencephalopathy (EHM), both severe threats to equine facilities. Different strains vary in their abortigenic and neuropathogenic potential and the simultaneous occurrence of EHM and abortion is rare. In this report, we present clinical observations collected during an EHV-1 outbreak caused by a so-called "neuropathogenic" EHV-1 G(2254)/D(752) polymerase (Pol) variant, which has become more prevalent in recent years and is less frequently associated with abortions. In this outbreak with 61 clinically affected horses, 6/7 pregnant mares aborted and 8 horses developed EHM. Three abortions occurred after development of EHM symptoms. Virus detection was performed by nested PCR targeting gB from nasal swabs (11 positive), blood serum (6 positive) and peripheral blood mononuclear cells (9 positive) of a total of 42 horses sampled. All 6 fetuses tested positive for EHV-1 by PCR and 4 by virus isolation. Paired serum neutralization test (SNT) on day 12 and 28 after the index case showed a significant (≥ 4-fold) increase in twelve horses (n = 42; 28.6%). This outbreak with abortions and EHM cases on a single equine facility provided a unique opportunity for the documentation of clinical disease progression as well as diagnostic procedures.


[Effect of benzo(a)pyrene on soil microbiocenosis].
The experimental studies have shown that benz(a)pyrene being in the soil affects the formation of soil microbiocenosis and biological activity of soils.


Surgical considerations in the management of tumours of the nose and paranasal sinuses in a Northern Nigerian Teaching Hospital.
Tumours of the nose and paranasal sinuses in sub-Saharan Africa are generally characterised by late presentation posing management challenges to the otorhinolaryngologists in the sub-region. To appraise surgical considerations in the management of tumours of the nose and paranasal sinuses in a developing nation from the experiences of an Ear, Nose, and Throat Department of a Nigerian Teaching Hospital. This was a chart review of patients with tumours of the nose and paranasal sinuses who underwent various surgical operations over a period of four and a half years.The patients were referred by other physicians or health care workers. They were assessed clinically, backed by laboratory and radiological investigations. A total number of 55 patients underwent 64 surgical operations. There were 31 (56.4%) males and 24 (43.6%) females, giving a male to female ratio of 1.3:1. They were aged between four years and 70 years. In 46(83.6%) patients the tumours had extended beyond the nasal cavity or one sinus cavity to contiguous structures. The surgical operations carried out were lateral rhinotomy in 37(57.8%), intranasal clearance and intranasal antrostomy in 16(25%), total maxillectomy in seven(11%), and anterior craniofacial resection in two (3.1%) patients.The histological examination showed that 43 (78.2%) cases were benign, while 12 (21.8%) cases were malignant. These malignant cases needed radiotherapy and chemotherapy. Majority of the cases were characterised by late presentation, requiring surgical approaches such as lateral rhinotomy, total maxillectomy or craniofacial resection depending on the extent of the tumour. Poverty, ignorance, inadequate funding and administration challenges of health resources are factors militating against proper clinical management of tumours of the nose and paranasal sinuses in developing nations. Provision of free medical care and modern facilities for early diagnosis, treatment, and health education are needed to reverse the trend.


Rapid Chemical Synthesis of Serine Protease Inhibitor Kazal-type 13 (SPINK13) Glycoform by a Combined Method with Glycan Insertion Strategy and Fast-Flow Fmoc SPPS.
Serine protease inhibitor Kazal type 13 (SPINK13) is a secreted protein that has been recently studied as a therapeutic drug and an interesting biomarker for cancer cells. Although SPINK13 has a consensus sequence (Pro-Asn-Val-Thr) for N-glycosylation, the existence of N-glycosylation and its functions are still unclear. In addition to this, the preparation of glycosylated SPINK 13 has not been examined by both the cell expression method and chemical synthesis. Herein we report the chemical synthesis of the scarce N-glycosylated form of SPINK13 by a rapid synthetic method combined with the chemical glycan insertion strategy and a fast-flow SPPS method. Glycosylated asparagine thioacid was designed to chemoselectively be inserted between two peptide segments where is the sterically bulky Pro-Asn(N-glycan)-Val junction by two coupling reactions which consist of diacyl disulfide coupling (DDC) and thioacid capture ligation (TCL). This insertion strategy successfully afforded the full-length polypeptide of SPINK13 within two steps from glycosylated asparagine thioacid. Because the two peptides used for this synthesis were prepared by a fast-flow SPPS, the total synthetic time of glycoprotein was considerably shortened. This synthetic concept enables us to repetitively synthesize a target glycoprotein easily. Folding experiments afforded well-folded structure confirmed by CD and disulfide bond map. Invasion assays of glycosylated SPINK13 and non-glycosylated SPINK13 with pancreatic cancer cells showed that non-glycosylated SPINK-13 was more potent than that of glycosylated SPINK13.


Outcome of self-expandable metallic stents in low-grade versus advanced hilar obstruction.
Self-expandable metallic stents (SEMS) are known to provide a longer patency time than plastic stents for malignant biliary obstructions including hilar obstruction. However, studies that focus on the efficacy of SEMS in low-grade and advanced hilar obstructions are still scanty. Ninety four patients with malignant hilar obstructions were enrolled (six were later excluded). Patients were divided into two groups according to their Bismuth levels. Group A were patients with Bismuth I (n = 53). Group B were patients with Bismuth II, III and IV (n = 35). Technical success, complications, jaundice resolution, stent patency time, and patients' survival were analyzed. Our intention-to-treat analysis showed that group A had a significant lower rate of post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis than group B; 16.1% versus 44.7%, (P < 0.01). Four patients from group B still had persistent jaundice. Our per protocol analysis demonstrated that median stent patency time in groups A and B were not statistically different (74 vs 60 days). Median survival time in groups A and B were also not statistically different (90 vs 75 days). In both groups, those without liver metastasis had significantly better patency and survival time than those with liver metastasis (P = 0.010 and 0.027, respectively). In patients with hilar obstruction, liver metastasis is one of the main factors that determine survival of the patient. Patency times of SEMS in both low-grade and advanced obstructions are comparable. However, in the advanced group, there is a significant risk of post-ERCP cholangitis.


Burns: dressings.
Burns are classified according to depth. This overview concerns the treatments for partial-thickness burns, which can be expected or have the potential to heal spontaneously (superficial partial-thickness and mid-dermal partial-thickness burns). Injuries that involve the deeper part of the dermis and require surgical treatments to achieve healing are not the focus of this overview. We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of treatments for partial-thickness burns? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this review). At this update, searching of electronic databases retrieved 322 studies. After deduplication and removal of conference abstracts, 193 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 160 studies and the further review of 33 full publications. Of the 33 full articles evaluated, two systematic reviews and two RCTs were added at this update. We performed a GRADE evaluation for 30 PICO combinations. In this systematic overview, we categorised the efficacy for 10 interventions, based on information relating to the effectiveness and safety of alginate dressing, biosynthetic dressing, chlorhexidine-impregnated paraffin gauze dressing, hydrocolloid dressing, hydrogel dressing, paraffin gauze dressing, polyurethane film, silicone-coated nylon dressing, silver-impregnated dressing, and silver sulfadiazine cream.


External validation of the Acute Physiology and Chronic Health Evaluation II in Korean intensive care units.
This study was designed to validate the usefulness of the Acute Physiology and Chronic Health Evaluation (APACHE) II for predicting hospital mortality of critically ill Korean patients. We analyzed data on 826 patients who had been admitted to nine intensive care units and were included in the Fever and Antipyretics in Critical Illness Evaluation study cohort. Among the patients enrolled, 62% (512/826) were medical and 38% (314/826) were surgical patients. The median APACHE II score was 17 (11 to 23 interquartile range), and the hospital mortality rate was 19.5%. Age, underlying diseases, medical patients, mechanical ventilation, and renal replacement therapy were independently associated with hospital mortality. The calibration of APACHE II was poor (H=57.54, p<0.0001; C=55.99, p<0.0001), and the discrimination was modest [area under the receiver operating characteristic (aROC)=0.729]. Calibration was poor for both medical and surgical patients (H=63.56, p<0.0001; C=73.83, p<0.0001, and H=33.92, p<0.0001; C=33.34, p=0.0001, respectively), while discrimination was poor for medical patients (aROC=0.651) and modest for surgical patients (aROC=0.704). At the predicted risk of 50%, APACHE II had a sensitivity of 36.6% and a specificity of 87.4% for hospital mortality. For Koreans, the APACHE II exhibits poor calibration and modest discrimination for hospital mortality. Therefore, a new model is needed to accurately predict mortality in critically ill Korean patients.


Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).
Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.


Dispersed and aggregated gap junction channels identified by immunogold labeling of freeze-fractured membranes.
An indirect immunogold labeling technique was applied to replicas of freeze-fractured membranes of rapidly frozen unfixed cells. The endogenous gap junction protein Cx43 of BICR/M1Rk rat mammary tumor cells was preferentially identified in quasi-crystalline gap junction plaques as were the transfected connexins Cx40, Cx43, and Cx45 in HeLa (human cervical carcinoma) cells. With this method we also detected contact areas with dispersed gap junction channels which are the only structural correlation for endogenous Cx45 in HeLa wild-type cells where no gap junction plaques exist. In double-transfected HeLa cells a colocalization of Cx40 and Cx43 was occasionally detected in quasi-crystalline gap junction plaques, whereas in contact areas with dispersed particles only one Cx type was present. Our results indicate that functional gap junction channels exist outside the quasi-crystalline plaques.


[Calcium antagonists in the urethral syndrome of women with urinary incontinence and urgency].
The action of the antagonists of the calcium was evaluated in the Urethral Syndrome of the woman (incontinence, urgency, disury). In 60 female's patients that went for urethral syndrome. I used the Cinarizina in 20 patients, and the Flunarizina in 20 patients. And in 20 patients were used placebo. In the patients that used Flunarizina and Cinarizina were observed a reduction of the urine incontinence, of the urgency, and the disury, the micturition was lingering and easy, the number of the micturitions decreased by the morning, compared with the patients that used placebo. The antagonists of the calcium can be useful in those patients with urethral syndrome especially the biggest women.


Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan.
Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country. In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin. Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required.


Detection of enthesitis in children with enthesitis-related arthritis: dolorimetry compared to ultrasonography.
To evaluate the distribution of enthesitis and the accuracy of physical examination with a dolorimeter for the detection of enthesitis in children, using ultrasound (US) assessment as the reference standard. We performed a prospective cross-sectional study of 30 patients with enthesitis-related arthritis (ERA) and 30 control subjects. The following tendon insertion sites were assessed by standardized physical examination with a dolorimeter and US: common extensor on the lateral humeral epicondyle, common flexor on the medial humeral epicondyle, quadriceps at the superior patella, patellar ligament at the inferior patella, Achilles, and plantar fascia at the calcaneus. Abnormal findings on US were detected most commonly at the insertion of the quadriceps (30% [18 of 60 sites]), common extensor (12% [7 of 60]), and Achilles (10% [6 of 60]) tendons. The intrarater reliability of US (kappa statistic) was 0.78 (95% confidence interval [95% CI] 0.63-0.93), and the interrater reliability was 0.81 (95% CI 0.67-0.95). Tenderness as detected by standardized dolorimeter examination had poor positive predictive value for US-confirmed enthesitis. In comparison to controls, patients with ERA reported more pain and had lower pain thresholds at every site, including control sites (P < 0.001 for all comparisons). The interrater reliability of dolorimeter examination for detection of enthesitis was low (κ = 0.49 [95% CI 0.33-0.65]). Compared to US, standardized dolorimeter examination for the detection of enthesitis in children has poor accuracy and reliability. The decreased pain threshold of ERA patients likely contributed to the limited accuracy of the physical examination findings. Further research regarding the utility of US for identifying enthesitis at diagnosis of juvenile idiopathic arthritis, accurately predicting disease progression, and guiding therapeutic decisions is warranted.


Perception of treatment burden, psychological distress, and fatigue in thyroid cancer patients and their partners - effects of gender, role, and time since diagnosis.
The aim of this study was to examine diagnosis and treatment burden as well as psychological distress (anxiety and depression) and fatigue in thyroid cancer patients and their partners, focusing on the effects of gender, role, and time since diagnosis. Seventy-one patients diagnosed and treated for differentiated thyroid cancer within the past 7 years, participated in this online study, as well as 40 partners. Standardized questionnaires were used rating anxiety, depression, fatigue, and quality of life. Suffering in the context of diagnosis and treatment was evaluated using numeric analog scales. Patients' most recent hormone status was integrated into analysis. Male and female patients but not their partners had significantly higher mean anxiety scores (p < 0.001) than the norm. Severe fatigue that warrants observation and treatment was reported by two of 21 male patients (9.5%), 12 of 50 female patients (24%), two of 28 male partners (7.1%), and no female partners. With respect to diagnosis and treatment burden, female partners expressed the highest burden, while male patients expressed the lowest. This burden was associated with current fatigue levels in male patients and with current anxiety, depression, and fatigue levels in female patients. Although both patients and partners suffer from the diagnosis and treatment of differentiated thyroid cancer, only patients are at risk of developing anxiety symptoms or fatigue. A simple question like 'How did being told you have thyroid cancer affect you?' might successfully screen for patients who are at risk.


Elemental and radionuclide exposures and uptakes by small rodents, invertebrates, and vegetation at active and post-production uranium mines in the Grand Canyon watershed.
The effects of breccia pipe uranium mining in the Grand Canyon watershed (Arizona) on ecological and cultural resources are largely unknown. We characterized the exposure of biota to uranium and co-occurring ore body elements during active ore production and at a site where ore production had recently concluded. Our results indicate that biota have taken up uranium and other elements (e.g., arsenic, cadmium, copper, molybdenum, uranium) from exposure to ore and surficial contamination, like blowing dust. Results indicate the potential for prolonged exposure to elements and radionuclides upon conclusion of active ore production. Mean radium-226 in deer mice was up to 4 times greater than uranium-234 and uranium-238 in those same samples; this may indicate a potential for, but does not necessarily imply, radium-226 toxicity. Soil screening benchmarks for uranium and molybdenum and other toxicity thresholds for arsenic, copper, selenium, uranium (e.g., growth effects) were exceeded in vegetation, invertebrates, and rodents (Peromyscus spp., Thomomys bottae, Tamias dorsalis, Dipodomys deserti). However, the prevalence and severity of microscopic lesions in rodent tissues (as direct evidence of biological effects of uptake and exposure) could not be definitively linked to mining. Our data indicate that land managers might consider factors like species, seasonal changes in environmental concentrations, and bioavailability, when determining mine permitting and remediation in the Grand Canyon watershed. Ultimately, our results will be useful for site-specific ecological risk analysis and can support future decisions regarding the mineral extraction withdrawal in the Grand Canyon watershed and elsewhere.


Evaluation of pulse crops' functional diversity supporting food production.
Pulses, defined as legumes which produce dry seed used for human consumption, are plants of great agronomic value, at the food system level as much as the field level but their diversity has been largely underused. This study aimed at analyzing existing data on cultivated pulse species in the literature to provide a broad and structured description of pulses' interspecific functional diversity. We used a functional trait-based approach to evaluate how pulse diversity could support food production in agroecosystems constrained by low water and nutrient availability and exposed to high weed pressure. We gathered data for 17 functional traits and six agroecosystem properties for 43 pulse species. Our analytical framework highlights the correlations and combinations of functional traits that best predict values of six agroecosystem properties defined as ecosystem services estimates. We show that pulse diversity has been structured both by breeding and by an environmental gradient. The covariance space corresponding to agroecosystem properties was structured by three properties: producers, competitors, stress-tolerant species. The distribution of crop species in this functional space reflected ecological adaptive strategies described in wild species, where the size-related axis of variation is separated from variation of leaf morpho-physiological traits. Six agroecosystem properties were predicted by different combinations of traits. However, we identified ubiquitous plant traits such as leaflet length, days to maturity, seed weight, and leaf nitrogen content, that discriminated agroecosystem properties and allowed us to gather individual species into three clusters, representative of the three strategies highlighted earlier. Implications for pulses provisioning of services in agroecosystems are discussed.


Syntheses of racemic and diastereomeric mixtures of 3,7,11,15-tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane, the cuticular tetramethylalkanes of the tsetse fly, Glossina brevipalpis.
Cuticular hydrocarbons of the tsetse fly, Glossina brevipalpis, contain 3,7,11,15-tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane as possible candidates for its contact sex pheromone. These were synthesized as racemic and diastereomeric mixtures starting from racemic citronellol and employing phenyl-sulfone-mediated chain-elongation as the key reaction.


Partial spin ordering and complex magnetic structure in BaYFeO4: a neutron diffraction and high temperature susceptibility study.
The novel iron-based compound, BaYFeO4, crystallizes in the Pnma space group with two distinct Fe(3+) sites, that are alternately corner-shared [FeO5](7-) square pyramids and [FeO6](9-) octahedra, forming into [Fe4O18](24-) rings, which propagate as columns along the b-axis. A recent report shows two discernible antiferromagnetic (AFM) transitions at 36 and 48 K in the susceptibility, yet heat capacity measurements reveal no magnetic phase transitions at these temperatures. An upturn in the magnetic susceptibility measurements up to 400 K suggests the presence of short-range magnetic behavior at higher temperatures. In this Article, variable-temperature neutron powder diffraction and high-temperature magnetic susceptibility measurements were performed to clarify the magnetic behavior. Neutron powder diffraction confirmed that the two magnetic transitions observed at 36 and 48 K are due to long-range magnetic order. Below 48 K, the magnetic structure was determined as a spin-density wave (SDW) with a propagation vector, k = (0, 0, (1)/3), and the moments along the b-axis, whereas the structure becomes an incommensurate cycloid [k = (0, 0, ∼0.35)] below 36 K with the moments within the bc-plane. However, for both cases the ordered moments on Fe(3+) are only of the order ∼3.0 μB, smaller than the expected values near 4.5 μB, indicating that significant components of the Fe moments remain paramagnetic to the lowest temperature studied, 6 K. Moreover, new high-temperature magnetic susceptibility measurements revealed a peak maximum at ∼550 K indicative of short-range spin correlations. It is postulated that most of the magnetic entropy is thus removed at high temperatures which could explain the absence of heat capacity anomalies at the long-range ordering temperatures. Published spin dimer calculations, which appear to suggest a k = (0, 0, 0) magnetic structure, and allow for neither low dimensionality nor geometric frustration, are inadequate to explain the observed complex magnetic structure.


Highly Ordered Small Molecule Organic Semiconductor Thin-Films Enabling Complex, High-Performance Multi-Junction Devices.
Organic semiconductors have opened up many new electronic applications, enabled by properties like flexibility, low-cost manufacturing, and biocompatibility, as well as improved ecological sustainability due to low energy use during manufacturing. Most current devices are made of highly disordered thin-films, leading to poor transport properties and, ultimately, reduced device performance as well. Here, we discuss techniques to prepare highly ordered thin-films of organic semiconductors to realize fast and highly efficient devices as well as novel device types. We discuss the various methods that can be implemented to achieve such highly ordered layers compatible with standard semiconductor manufacturing processes and suitable for complex devices. A special focus is put on approaches utilizing thermal treatment of amorphous layers of small molecules to create crystalline thin-films. This technique has first been demonstrated for rubrene─an organic semiconductor with excellent transport properties─and extended to some other molecular structures. We discuss recent experiments that show that these highly ordered layers show excellent lateral and vertical mobilities and can be electrically doped to achieve high n- and p-type conductivities. With these achievements, it is possible to integrate these highly ordered layers into specialized devices, such as high-frequency diodes or completely new device principles for organics, e.g., bipolar transistors.


Anomia for facial expressions: neuropsychological mechanisms and anatomical correlates.
We report a patient with a selective impairment in naming and pointing to emotional facial expressions following a circumscribed lesion of the right temporal lobe. Detailed investigation of this patient's deficit revealed that the neuropsychological mechanism underlying his anomia for facial expressions is best understood as a category-specific bidirectional visual-verbal disconnection between intact visual semantic and verbal semantic representations for facial emotions. Magnetic resonance imaging findings from this case and from another patient previously described with this unique syndrome (Rapcsak, Kaszniak, & Rubens, 1989), together with the results of cortical electrical stimulation studies and microelectrode recordings of cortical neuronal activity in epileptic patients, provide converging evidence that the inferotemporal visual association cortex of the right middle temporal gyrus plays an important functional role in the verbal labeling of emotional facial expressions. The implications of these findings for cognitive and neural models of facial affect processing are discussed.


Odd-electron-bonded sulfur radical cations: X-ray structural evidence of a sulfur-sulfur three-electron σ-bond.
The one-electron oxidations of 1,8-chalcogen naphthalenes Nap(SPh)2 (1) and Nap(SPh)(SePh) (2) lead to the formation of persistent radical cations 1(•+) and 2(•+) in solution. EPR spectra, UV-vis absorptions, and DFT calculations show a three-electron σ-bond in both cations. The former cation remains stable in the solid state, while the latter dimerizes upon crystallization and returns to being radical cations upon dissolution. This work provides conclusive structural evidence of a sulfur-sulfur three-electron σ-bond (in 1(•+)) and a rare example of a persistent heteroatomic three-electron σ-bond (in 2(•+)).


Urinary bladder fibromas in dogs: 51 cases (1981-1985).
Between Jan 1, 1981, and June 30, 1985, fibromas were diagnosed in tissues removed from the urinary bladders of 51 dogs. Hematuria, the most common clinical sign, was associated with the fibromas in 47 of 50 cases. Most dogs responded well to surgical excision of the neoplasms, with rapid resolution of the hematuria followed by long periods without abnormal clinical signs. Three dogs were euthanatized because of continuing or recurrent clinical problems, which included bladder dysfunction. One dog required continuing medication with antibiotics and corticosteroids to control hematuria.


The regulation of Moco biosynthesis and molybdoenzyme gene expression by molybdenum and iron in bacteria.
Bacterial molybdoenzymes are key enzymes involved in the global sulphur, nitrogen and carbon cycles. These enzymes require the insertion of the molybdenum cofactor (Moco) into their active sites and are able to catalyse a large range of redox-reactions. Escherichia coli harbours nineteen different molybdoenzymes that require a tight regulation of their synthesis according to substrate availability, oxygen availability and the cellular concentration of molybdenum and iron. The synthesis and assembly of active molybdoenzymes are regulated at the level of transcription of the structural genes and of translation in addition to the genes involved in Moco biosynthesis. The action of global transcriptional regulators like FNR, NarXL/QP, Fur and ArcA and their roles on the expression of these genes is described in detail. In this review we focus on what is known about the molybdenum- and iron-dependent regulation of molybdoenzyme and Moco biosynthesis genes in the model organism E. coli. The gene regulation in E. coli is compared to two other well studied model organisms Rhodobacter capsulatus and Shewanella oneidensis.


Granulopoiesis in tadpoles of Rana esculenta. Ultrastructural observations on the developing granulocytes and on the development of eosinophil granules.
The morphology and development of the granules of developing eosinophils present in the trunk kidneys of Rana esculenta tadpoles has been studied at the ultrastructural level. During the differentiation of eosinophil granulocytes a single and morphologically unique population of cytoplasmic granules is present. Fully developed granules are spherical, membrane-limited, and have a dense and homogeneous content. Eosinophil granules have been traced back to Golgi-derived vacuoles which fuse and form immature granules containing a dense and knot-like precipitate. By condensation these immature granules transform into the definitive homogeneous forms. The eosinophil granules of Rana esculenta are compared to those in other vertebrates and possible phylogenetic aspects are discussed.


Structural basis for non-genuine phenolic acceptor substrate specificity of Streptomyces roseochromogenes prenyltransferase CloQ from the ABBA/PT-barrel superfamily.
Acceptor substrate specificity of Streptomyces roseochromogenes prenyltransferase SrCloQ was investigated using different non-genuine phenolic compounds. RP-UHPLC-UV-MSn was used for the tentative annotation and quantification of the prenylated products. Flavonoids, isoflavonoids and stilbenoids with different types of substitution were prenylated by SrCloQ, although with less efficiency than the genuine substrate 4-hydroxyphenylpyruvate. The isoflavan equol, followed by the flavone 7,4'-dihydroxyflavone, were the best non-genuine acceptor substrates. B-ring C-prenylation was in general preferred over A-ring C-prenylation (ratio 5:1). Docking studies of non-genuine acceptor substrates with the B-ring oriented towards the donor substrate dimethylallyl pyrophosphate, showed that the carbonyl group of the C-ring was able to make stabilizing interactions with the residue Arg160, which might determine the preference observed for B-ring prenylation. No reaction products were formed when the acceptor substrate had no phenolic hydroxyl groups. This preference can be explained by the essential hydrogen bond needed between a phenolic hydroxyl group and the residue Glu281. Acceptor substrates with an additional hydroxyl group at the C3' position (B-ring), were mainly O3'-prenylated (> 80% of the reaction products). This can be explained by the proximity of the C3' hydroxyl group to the donor substrate at the catalytic site. Flavones were preferred over isoflavones by SrCloQ. Docking studies suggested that the orientation of the B-ring and of the phenolic hydroxyl group at position C7 (A-ring) of flavones towards the residue Tyr233 plays an important role in this observed preference. Finally, the insights obtained on acceptor substrate specificity and regioselectivity for SrCloQ were extended to other prenyltransferases from the CloQ/NhpB family.


[A case of primary progressive multiple sclerosis with onset of memory impairment].
We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS) presenting with chronic progressive memory impairment. From a couple of years prior to admission, she had developed impairment of her short-term memory. For example, she forgot her nephew's name, and spoke the same phrases again and again. She also sometimes forgot to turn off her gas stove and forgot things she bought in shops. Moreover, her mental activity gradually decreased and she became apathetic. However, she did not note her memory impairment, and had no hallucinations. She was admitted to our hospital on 20 May, 2003 because donepezil had been ineffective for treating her memory impairment. Neurologically, she showed bilateral horizontal gaze nystagmus, mild limb ataxia on the left and mildly ataxic gait. Neuropsychological examinations showed mildly impaired cognitive function, e.g., MMSE 25/30, WAIS-R full IQ 69 and especially in verbal short memory, which may represent temporal lobe dysfunction. Moreover, Benton's visual memory test revealed marked visual short-term memory impairment, while impaired performance on a Kana picking up test suggested mild to moderate attention impairment, which could have represented frontal lobe dysfunction. Brain MRI showed multiple T2-high plaque lesions close to the bilateral lateral ventricles, and bilateral optic nerve lesions enhanced by gadolinium. Also, spinal cord MRI showed a gadolinium enhanced lesion at Th5 on the left. Cerebral spinal fluid (CSF) examination showed normal cell count and protein level, and undetectable oligoclonal bands (OCB), but an elevated IgG index (1.1, normal < 0.85). Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally, indicating subclinical optic nerve lesions. She was thus diagnosed as having PPMS according to McDonald's diagnostic criteria for MS. 99mTc Single photon emission computed tomography (SPECT) showed a decreased cerebral blood flow (CBF) in the bilateral frontal and temporal lobes, which was consistent with her clinical features. PPMS patients generally present with chronic progressive spastic paraparesis and/or cerebellar ataxia. Cognitive impairments observed in PPMS are generally thought to be due to white matter lesions, i.e., subcortical dementia. However, some recent reports have shown MS patients with short-term memory impairment (antegrade amnesia) similar to cortical dementias such as Alzheimer's disease (AD). In such MS cases, visual short-term memory impairment seems characteristic of their cognitive impairment compared to AD cases. As well, the present case showed visual memory impairment as evaluated by Benton's memory test. Parietal and frontal lobes are reported to be important for verbal and visual working memory, respectively. Thus, in the present case, decreased CBF in the frontal and temporal lobes, which could have been due to a disconnection between cortices and subcortices caused by the white matter lesions, is consistent with the type of her cognitive dysfunction, i.e., notable visual memory impairment. PPMS may thus be an important disease as a differential diagnosis for chronic progressive dementia. Further neuropsychological and functional imaging studies will be necessary to achieve a better understanding of the mechanisms of cognitive impairment in PPMS.


[Approach to the primary mass and neck in lower lip cancers: analysis of 24 cases].
In this study, we analyzed the surgical approach which we carried out for treatment of the primary mass and neck in 24 lower lip cancer cases and its results. 24 patients (5 females, 19 males; mean age 56.8; range 41 to 72 years) who were operated on in our clinic for lip cancer between March 1995 and March 2007 and whom we were able to long term follow-up were included in this study. Tumor was resected with 1-2 cm surgical margin in all cases. The tissue defect was reconstructed by either primary closure or local/regional flaps. If the tumor was located in the middle of the lip, bilateral neck dissection, otherwise unilateral neck dissection was performed. Postoperative radiotherapy was used in cases who had neck metastatic disease. Functional results were evaluated regarding recurrence and mortality rates during five-year mean follow-up period. Tumor was originated from the lower lip alone in 20 cases. There was secondary commissure involvement in four cases. According to the TNM (tumor, node, metastasis) classification (AJCC, 2002), distribution of the cases was T1N0M0 (n=10), T2N0M0 (n=9), T3N1M0 (n=3), T4N2aM0 (n=1), T4N2cM0 (n=1). Primary closure (n=7), Abbe-Estlander flap (n=9), Karapandzic flap (n=4), Melolabial flap (n=3), Fan flap (n=1), pectoralis major myocutaneous flap (n=2) were used as reconstruction techniques. Histopathologically, metastatic disease was determined in the neck in four cases. During the follow-up period, there occurred ocal recurrence in two cases and regional metastasis in one. Two cases with distant metastasis died. Survival rates without illness for early and advanced stage tumors were 100% and 20%, respectively. Functional results after reconstruction were satisfactory, except in two cases which we used pectoralis major myocutaneous flap for reconstruction. Five-years survival rates without illness were significantly lower in cases with advanced stage tumor and N positive neck. This result indicates that stage of the tumor and neck involvement have a significant effect on prognosis. Furthermore, more satisfactory functional results were achieved in early stage tumors.


Depression and Anxiety in Women During Pregnancy in Slovenia.
The aim of the study was to evaluate the prevalence of elevated depression and anxiety among pregnant women and to examine its correlation with medical complications and socio-demographic characteristics. The study is based on a cross-sectional design of a sample of 348 women in three trimesters of pregnancy who received routine obstetrical care at the University Medical Centre Ljubljana, Department of Obstetrics and Gynaecology. The responding women filled out a questionnaire on socio-demographic variables, the Centre for Epidemiologic Studies Depression Scale CES-D and the State Trait Anxiety Inventory STAI. 21.7% of pregnant women were identified as suffering from elevated depression symptomatology, 15.7% reported high state anxiety and 12.5% had high trait anxiety. No significant differences in depression and anxiety across pregnancy trimesters were found. The women who have suffered from health complications during previous pregnancies showed higher state anxiety; those experiencing complications during their current pregnancy reported more intense symptoms of depression and of state and trait anxiety than women free of complications. Less educated, lower income and mothers of many children in the third pregnancy trimester reported more intensive symptoms of depression and trait anxiety. Elevated depression and anxiety are frequent among pregnant women. The results draw attention to the need for early detection and treatment of depression and anxiety during pregnancy.


Addition of aspirin to venous thromboembolism chemoprophylaxis safely decreases venous thromboembolism rates in trauma patients.
Trauma patients exhibit a multifactorial hypercoagulable state and have increased risk of venous thromboembolism (VTE). Despite early and aggressive chemoprophylaxis (CP) with various heparin compounds ("standard" CP; sCP), VTE rates remain high. In high-quality studies, aspirin has been shown to decrease VTE in postoperative elective surgical and orthopedic trauma patients. We hypothesized that inhibiting platelet function with aspirin as an adjunct to sCP would reduce the risk of VTE in trauma patients. We performed a retrospective observational study of prospectively collected data from all adult patients admitted to an American College of Surgeons Level I Trauma center from January 2012 to June 2015 to evaluate the addition of aspirin (sCP+A) to sCP regimens for VTE mitigation. Cox proportional hazard models were used to assess the potential benefit of adjunctive aspirin for symptomatic VTE incidence. 10,532 patients, median age 44 (IQR 28 to 62), 68% male, 89% blunt mechanism of injury, with a median Injury Severity Score (ISS) of 12 (IQR 9 to 19), were included in the study. 8646 (82%) of patients received only sCP, whereas 1886 (18%) patients received sCP+A. The sCP+A cohort displayed a higher median ISS compared with sCP (13 vs 11; p<0.01). The overall median time of sCP initiation was hospital day 1 (IQR 0.8 to 2) and the median day for aspirin initiation was hospital day 3 (IQR 1 to 6) for the sCP+A cohort. 353 patients (3.4%) developed symptomatic VTE. Aspirin administration was independently associated with a decreased relative hazard of VTE (HR 0.57; 95% CI 0.36 to 0.88; p=0.01). There were no increased bleeding or wound complications associated with sCP+A (point estimate 1.23, 95% CI 0.68 to 2.2, p=0.50). In this large trauma cohort, adjunctive aspirin was independently associated with a significant reduction in VTE and may represent a potential strategy to safely mitigate VTE risk in trauma patients. Further prospective studies evaluating the addition of aspirin to heparinoid-based VTE chemoprophylaxis regimens should be sought. Level III/therapeutic.


Expression of cellular isoform of prion protein on the surface of peripheral blood lymphocytes among women exposed to low doses of ionizing radiation.
Ionizing radiation affects the expression of adhesive and co-stimulatory molecules in lymphocytes. The physiological function of cellular isoform of prion protein (PrPc) is little known. Evidences indicate a link between lymphocytes activation and PrPc expression on their surface; however, no direct effect of radiation on PrPc level in these cells was investigated. The objective of this study was to determinate the effect of low doses of ionizing radiation on the expression of PrPc on the surface peripheral blood lymphocytes in the women operating X-ray equipment. In 36 female workers and 30 persons of the control group the PrPc expression on CD3 (T lymphocytes), CD4 (T helper), CD8 (T cytotoxic) and CD19 (B lymphocytes), as well as the percentage of lymphocytes with PrPc on their surface, were tested. Subgroups with respect to age and length of employment were selected. A significant increase was observed in PrPc expression on CD3 and CD4 with lowered PrPc level on CD8 and percentage of CD8 cells with PrPc in workers compared to control. The PrPc level did not show significant changes in subgroups in relation to age (below and over 40 years old) both in the investigated and control groups, whereas a lower percentage of PrPc expressing CD19 cells showed in employed women below 40 years of age. A significant decrease was found in PrPc expression on the surface of CD3, CD4 and CD8 cells in the subgroup employed for over 10 years than in the subgroup with less than 10 years of employment.


Larvicidal, Repellent, and Irritant Potential of the Seed-Derived Essential oil of Apium graveolens Against Dengue Vector, Aedes aegypti L. (Diptera: Culicidae).
Aedes aegypti L. is one of the primary disease vectors spreading various dreadful diseases throughout the world, specifically over tropics and subtropics. Keeping in view the adverse effects of chemical insecticides-based intervention measures, the eco-friendly and bio-degradable essential oil extracted from the seeds of celery, Apium graveolens were investigated for its efficacy against Ae. aegypti. Larvicidal bioassay carried out with the seed oil against early fourth instars of Ae. aegypti caused an LC50 and LC90 values of 16.10 and 29.08 ppm, respectively, after an exposure to 24 h. The cidal effect of the celery seed oil augmented by 1.2-fold; after an exposure to 48 h; revealing an LC50 value of 13.22 ppm. Interestingly, the seed oil did not cause immediate larval mortality, suggesting a delayed toxicity against the larval stage. Present investigations also revealed remarkable effective repellency of the oil leading to 100% protection till 165 min as compared to control that did not result in any repellency against adult Ae. aegypti. Interestingly, only one bite was recorded in the 165th-min after which only two bites were scored until 180 min of exposure of the adult mosquitoes to the oil. An exciting observation was that the knocked-down effect in adults exposed to 10% oil-impregnated papers. The contact irritancy assays with paper impregnated with 1% celery seed oil caused first flight only after 4 s resulting in an average of 63.66 flights during 15 min of exposure revealing the relative irritability of 26.97. The qualitative phytochemical analysis of the seed oil showed the presence of flavonoids, lactones, and terpenoids as the major constituents suggesting their probable role in the toxicity. Our results confirmed that celery seed essential oil can be used as an efficient larvicide and repellent against Ae. aegypti. The identification of the bioactive components, their mode of action, and studying effects on non-target organisms and the environment would help in devising mosquito-management strategies.


Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases.
Protein-truncating variants (PTVs) near the 3' end of genes may escape nonsense-mediated decay (NMD). PTVs in the NMD-escape region (PTVescs) can cause Mendelian disease but are difficult to interpret given their varying impact on protein function. Previously, PTVesc burden was assessed in an epilepsy cohort, but no large-scale analysis has systematically evaluated these variants in rare disease. We performed a retrospective analysis of 29,031 neurodevelopmental disorder (NDD) parent-offspring trios referred for clinical exome sequencing to identify PTVesc de novo mutations (DNMs). We identified 1,376 PTVesc DNMs and 133 genes that were significantly enriched (binomial p < 0.001). The PTVesc-enriched genes included those with PTVescs previously described to cause dominant Mendelian disease (e.g., SEMA6B, PPM1D, and DAGLA). We annotated ClinVar variants for PTVescs and identified 948 genes with at least one high-confidence pathogenic variant. Twenty-two known Mendelian PTVesc-enriched genes had no prior evidence of PTVesc-associated disease. We found 22 additional PTVesc-enriched genes that are not well established to be associated with Mendelian disease, several of which showed phenotypic similarity between individuals harboring PTVesc variants in the same gene. Four individuals with PTVesc mutations in RAB1A had similar phenotypes including NDD and spasticity. PTVesc mutations in IRF2BP1 were found in two individuals who each had severe immunodeficiency manifesting in NDD. Three individuals with PTVesc mutations in LDB1 all had NDD and multiple congenital anomalies. Using a large-scale, systematic analysis of DNMs, we extend the mutation spectrum for known Mendelian disease-associated genes and identify potentially novel disease-associated genes.


First complete sauropod dinosaur skull from the Cretaceous of the Americas and the evolution of sauropod dentition.
Sauropod dinosaur bones are common in Mesozoic terrestrial sediments, but sauropod skulls are exceedingly rare--cranial materials are known for less than one third of sauropod genera and even fewer are known from complete skulls. Here we describe the first complete sauropod skull from the Cretaceous of the Americas, Abydosaurus mcintoshi, n. gen., n. sp., known from 104.46 +/- 0.95 Ma (megannum) sediments from Dinosaur National Monument, USA. Abydosaurus shares close ancestry with Brachiosaurus, which appeared in the fossil record ca. 45 million years earlier and had substantially broader teeth. A survey of tooth shape in sauropodomorphs demonstrates that sauropods evolved broad crowns during the Early Jurassic but did not evolve narrow crowns until the Late Jurassic, when they occupied their greatest range of crown breadths. During the Cretaceous, brachiosaurids and other lineages independently underwent a marked diminution in tooth breadth, and before the latest Cretaceous broad-crowned sauropods were extinct on all continental landmasses. Differential survival and diversification of narrow-crowned sauropods in the Late Cretaceous appears to be a directed trend that was not correlated with changes in plant diversity or abundance, but may signal a shift towards elevated tooth replacement rates and high-wear dentition. Sauropods lacked many of the complex herbivorous adaptations present within contemporaneous ornithischian herbivores, such as beaks, cheeks, kinesis, and heterodonty. The spartan design of sauropod skulls may be related to their remarkably small size--sauropod skulls account for only 1/200th of total body volume compared to 1/30th body volume in ornithopod dinosaurs.


EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units.
Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case-control studies and consists of a two-step process in which the difference in Pearson's correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair.


[Sonographic diagnosis of complicated peptic ulcer].
The sensitivity of sonography was assessed in an unselected series of 56 patients suffering from complicated gastric (20) or duodenal (36) ulcers. Evidence of ingested material and/or free gas in the peritoneal cavity associated with a pathologic gastroduodenal cockade proves perforation. Ulcer penetration is visible as eccentric "tumour" extension into hepatoduodenal ligament, liver or pancreas, whereas callous ulcer is recognisable as pathologic noninfiltrating cockade, and duodenal obstruction from stomach distention in spite of fasting. Based on these criteria, immediate diagnosis was feasible in 42/56 patients (approximately 75%). Ulcer perforation was confirmed in 20/26 (approximately 77%), including plain x-ray negative cases, which comprised approximately 31% of the perforations in this series. Ulcer penetration and - obstruction and chronic callous ulcers were diagnosed in 22/30 (approximately 73%) patients. Thus, sonography was proven to be highly contributive to immediate diagnostic fact finding and therapy.


RT-PCR analysis of MMP-9 expression in human articular cartilage chondrocytes and synovial fluid cells.
This report presents a method for analyzing matrix metalloproteinase-9 (92 kD gelatinase) MMP-9 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR). With this method, chondrocytes isolated from small samples of osteoarthritic cartilage showed significantly elevated signal for MMP-9 mRNA compared to normal cartilage. In addition, cells of synovial fluid samples aspirated from osteoarthritic joints also exhibited MMP-9 expression using this technique. RT-PCR proved to be a sensitive method for assessing MMP-9 regulation in osteoarthritic and normal cartilage, and may provide a useful index of arthritic cartilage and synovial fluid cell metabolism when limited tissue is available.


Regulation of glycoprotein hormone alpha-subunit gene expression.
The appropriate, regulated expression of the glycoprotein hormone subunit genes is required to enable the biosynthesis of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and chorionic gonadotropin. We have focused our attention on mechanisms mediating regulated transcription of the common alpha-subunit gene. Our studies have examined both the signaling mechanisms and the DNA elements and transcription factors that are important for alpha-subunit expression. Our initial efforts involved characterization of DNA elements of the alpha-subunit gene important for basal and GnRH-stimulated expression. Clustered point mutation analysis identified two different, unrelated sequences that play a role in alpha-subunit transcription. When tested as multiple copies on a minimal promoter, one of these elements was sufficient to permit a response to GnRH, while the other enhanced basal expression. Therefore, we designated these DNA elements as the GnRH-response element (GnRH-RE) and the pituitary glycoprotein hormone basal element (PGBE), respectively. The GnRH-RE contains a consensus binding site for the Ets family of transcription factors. As several Ets factors have been shown to mediate transcriptional responses to the mitogen-activated protein kinase (MAPK) pathway, we investigated the possibility that GnRH effects on alpha-subunit transcription may involve the MAPK cascade. We found that GnRH can indeed activate MAPK and that MAPK activation is sufficient and necessary for transcriptional activation of the alpha-subunit gene. Efforts to further characterize proteins that interact with the PGBE led to the cloning of a LIM-homeodomain transcription factor designated LH-2. Recombinant LH-2 selectively binds to the PGBE in vitro. Transfection experiments have shown that an expression vector for LH-2 can activate the alpha-subunit promoter in heterologous cells. LH-2 appears to be a component of the endogenous factors that bind to the PGBE. Thus, LH-2 appears to be an excellent candidate as a factor responsible for basal expression of the alpha-subunit gene. Overall, these studies have contributed to identification of molecular components important for regulated expression of the glycoprotein hormone alpha-subunit gene.


Excretion of (14)C-fumonisin B(1), (14)C-hydrolyzed fumonisin B(1), and (14)C-fumonisin B(1)-fructose in rats.
14C-Fumonisin B(1) (FB(1)) was produced by Fusarium proliferatum M-5991 in modified Myro liquid medium and purified to >95% purity with a specific activity of 1.7 mCi/mmol. Nine male and nine female F344/N rats were each dosed by gavage with 0.69 micromol of (14)C-FB(1), (14)C-hydrolyzed FB(1), or (14)C-FB(1)-fructose/kg body weight. Urinary excretion of (14)C-FB(1) and (14)C-FB(1)-fructose was 0.5% and 4.4% of the total dose, respectively, and was similar between male and female rats. Urinary excretion of (14)C-hydrolyzed HFB(1) was significantly greater (P > 0.05) in female rats as compared with male rats (17.3% vs 12.8% of the total dose, respectively). There were no significant (P > 0.05) differences in biliary excretion of the three fumonisin compounds with a mean of 1. 4% of the dose excreted at 4 h after dosing. Lesser amounts continued to be excreted up to 9.25 h after dosing. Although biliary excretion of the (14)C-FB(1), (14)C-hydrolyzed FB(1), and (14)C-FB(1)-fructose was similar, increased urinary excretion of the (14)C-hydrolyzed FB(1) as compared to (14)C-FB(1) and (14)C-FB(1)-fructose indicated a greater absorption of the hydrolyzed form.


Geographical information systems as a tool for monitoring tobacco industry advertising.
Although the use of a geographical information systems (GIS) approach is usually applied to epidemiological disease outbreaks and environmental exposure mapping, it has significant potential as a tobacco control research tool in monitoring point-of-purchase (POP) tobacco advertising. An ecological study design approach was applied so as to primarily evaluate and interpret the spatial density and intensity of POP and tobacco industry advertisements within <300 m to high schools in Greece with the application of GIS methodology combining mapping, photographing and global positioning data. The GIS approach identified 133 POP and 44 billboards within 300 m of the school gates of Heraklion schools. On average 13 POP (range 4-21) and 4.4 billboards (range 1-9) were located per school, and all had at least 1 POP within 20 m of the school gate. On average (SD) 9 (6) tobacco advertisements per POP (range 0-25) were noted, and 80% of them were below child height. The GIS protocol identified that kiosks, that were excepted from the Greek ban on tobacco advertising, in comparison to other POP, were found not only to be closer and visible from the school gates (44.1% vs 10.8%, p<0.001) but were also found to have more external advertisements (8 (5) vs 5 (3), p<0.001). This study demonstrates the effectiveness of a GIS system in monitoring tobacco industry advertising on a large population-based scale and implies its use as a standardised method for monitoring tobacco industry strategies and tobacco control efforts.


Apparent auditory source width insensitivity in older hearing-impaired individuals.
Previous studies have shown a loss in the precision of horizontal localization responses of older hearing-impaired (HI) individuals, along with potentially poorer neural representations of sound-source location. These deficits could be the result or corollary of greater difficulties in discriminating spatial images, and the insensitivity to punctate sound sources. This hypothesis was tested in three headphone-presentation experiments varying interaural coherence (IC), the cue most associated with apparent auditory source width. First, thresholds for differences in IC were measured for a broad sampling of participants. Older HI participants were significantly worse at discriminating IC across reference values than younger normal-hearing participants. These results are consistent with senescent increases in temporal jitter. Performance decreased with age, a finding corroborated in a second discrimination experiment using a separate group of participants matched for hearing loss. This group also completed a third, visual experiment, with both a cross-mapping task where they drew the size of the sound they heard and the identification task where they chose the image that best corresponded to what they heard. The results from the visual tasks indicate that older HI individuals do not hear punctate images and are relatively insensitive to changes in width based on IC.


Nitrosation and oxidation in the regulation of gene expression.
A growing body of evidence suggests that the cellular response to oxidative and nitrosative stress is primarily regulated at the level of transcription. Posttranslational modification of transcription factors may provide a mechanism by which cells sense these redox changes. In bacteria, for example, OxyR senses redox-related changes via oxidation or nitrosylation of a free thiol in the DNA binding region. This mode of regulation may serve as a paradigm for redox-sensing by eukaryotic transcription factors as most-including NF-kappaB, AP-1, and p53-contain reactive thiols in their DNA binding regions, the modification of which alters binding in vitro. Several of these transcription factors have been found to be sensitive to both reactive oxygen species and nitric oxide-related species in vivo. It remains entirely unclear, however, if oxidation or nitrosylation of eukaryotic transcription factors is an important mode of regulation, or whether transcriptional activating pathways are principally controlled at other redox-sensitive levels.-Marshall, H. E., Merchant, K., Stamler, J. S. Nitrosation and oxidation in the regulation of gene expression.


Two-Stage Sparse Representation Clustering for Dynamic Data Streams.
Data streams are a potentially unbounded sequence of data objects, and the clustering of such data is an effective way of identifying their underlying patterns. Existing data stream clustering algorithms face two critical issues: 1) evaluating the relationship among data objects with individual landmark windows of fixed size and 2) passing useful knowledge from previous landmark windows to the current landmark window. Based on sparse representation techniques, this article proposes a two-stage sparse representation clustering (TSSRC) method. The novelty of the proposed TSSRC algorithm comes from evaluating the effective relationship among data objects in the landmark windows with an accurate number of clusters. First, the proposed algorithm evaluates the relationship among data objects using sparse representation techniques. The dictionary and sparse representations are iteratively updated by solving a convex optimization problem. Second, the proposed TSSRC algorithm presents a dictionary initialization strategy that seeks representative data objects by making full use of the sparse representation results. This efficiently passes previously learned knowledge to the current landmark window over time. Moreover, the convergence and sparse stability of TSSRC can be theoretically guaranteed in continuous landmark windows under certain conditions. Experimental results on benchmark datasets demonstrate the effectiveness and robustness of TSSRC.


Psychometric detection of schizotypy: perceptual aberration and physical anhedonia in relatives of schizophrenics.
We administered scales of Perceptual Aberration (PERAB) and Physical Anhedonia (PHYSAN), traits that may be related to risk for schizophrenia, to 54 schizophrenics, 146 of their first-degree relatives (evaluated for schizophrenia-related disorders), and 178 normal subjects (screened for psychotic disorders in them or their relatives). For both scales, there was a significant effect of group membership. For the PERAB scale, the schizophrenics had higher scores than the normal subjects, who had higher scores than the relatives. For the PHYSAN scale, schizophrenics had higher scores than their relatives, who had higher scores than the normal subjects. Patterns of familial correlations also suggested that physical anhedonia, but not perceptual aberration, may be familial among schizophrenics and their relatives. The PHYSAN scale, but not the PERAB one, may be a useful indicator of liability for schizophrenia among the relatives of affected probands.


Small-Conductance Ca2+-Activated K+ Channel 2 in the Dorsal Horn of Spinal Cord Participates in Visceral Hypersensitivity in Rats.
Visceral hypersensitivity is a highly complex and subjective phenomenon associated with multiple levels of the nervous system and a wide range of neurotransmission. The dorsal horn (DH) in spinal cord relays the peripheral sensory information into the brain. Small conductance Ca2+-activated K+ (SK) channels regulate neuronal excitability and firing by allowing K+ to efflux in response to increase in the intracellular Ca2+ level. In this study, we examined the influence of SK2 channels in the spinal DH on the pathogenesis of visceral hypersensitivity induced by colorectal distension (CRD) in rats. Electrophysiological results showed that rats with visceral hypersensitivity presented a decrease in the SK channel-mediated afterhyperpolarization current (IAHP), and an increase in neuronal firing rates and c-Fos positive staining in the spinal DH. Western blot data revealed a decrease in the SK2 channel protein in the membrane fraction. Moreover, intrathecal administration of the SK2 channel activator 1-EBIO or CyPPA alleviated visceral hypersensitivity, reversed the decrease in IAHP and the increase in neuronal firing rates in spinal DH in rats that experienced CRD. 1-EBIO or CyPPA effect could be prevented by SK2 channel blocker apamin. CRD induced an increase in c-Fos protein expression in the spinal DH, which was prevented by 1-EBIO. Together, these data suggest that visceral hypersensitivity and pain is associated with a decrease in the number and function of membrane SK2 channels in the spinal DH. Pharmacological manipulation of SK2 channels may open a new avenue for the treatment of visceral hypersensitivity and pain. Highlights: -Neonatal colorectal distension induced visceral hypersensitivity in rats.-Visceral hypersensitivity rats presented a decrease in afterhyperpolarization current (IAHP) and membrane SK2 channel protein in the spinal dorsal horn.-Visceral hypersensitivity rats presented an increase in neuronal firing rate in the spinal dorsal horn.-Intrathecal administration of SK2 channel activator 1-EBIO or CyPPA prevented visceral hypersensitivity and decrease in IAHP.


Population and colony structure and morphometrics in the queen dimorphic little black ant, Monomorium sp. AZ-02, with a review of queen phenotypes in the genus Monomorium.
The North American little black ant, Monomorium sp. AZ-02 (subfamily Myrmicinae), displays a dimorphism that consists of alate (winged) and ergatoid (wingless) queens. Surveys at our field site in southcentral Arizona, USA, demonstrated that only one queen phenotype (alate or ergatoid) occurred in each colony during the season in which reproductive sexuals were produced. A morphometric analysis demonstrated that ergatoid queens retained all specialized anatomical features of alate queens (except for wings), and that they were significantly smaller and had a lower mass than alate queens. Using eight morphological characters, a discriminant analysis correctly categorized all queens (40 of 40) of both phenotypes. A molecular phylogeny using 420 base pairs of the mitochondrial gene cytochrome oxidase I demonstrated that alate and ergatoid queens are two alternative phenotypes within the species; both phenotypes were intermixed on our phylogeny, and both phenotypes often displayed the same haplotype. A survey of the genus Monomorium (358 species) found that wingless queens (ergatoid queens, brachypterous queens) occur in 42 of 137 species (30.6%) in which the queen has been described. These wingless queen species are geographically and taxonomically widespread as they occur on several continents and in eight species groups, suggesting that winglessness probably arose independently on many occasions in the genus.


Model-Based Estimates of HIV Acquisition Due to Prison Rape.
Nearly 1.4 million men are incarcerated in federal and state prisons in the United States. These men are disproportionately affected by HIV in comparison with the at-large male population. The elevated prevalence of HIV infection in U.S. prisons has raised concerns over the potential for intraprison HIV transmission due to rape and other forms of sexual victimization. However, the number of men who acquire HIV after being raped in U.S. prisons is not known. We developed a mathematical model of HIV transmission to estimate the likelihood that an incarcerated man would become infected as a result of prison rape and to provide preliminary estimates of the number of prison rape victims who acquire HIV. Our results suggest that between 43 and 93 currently incarcerated men already have or will acquire HIV as a result of being raped in prison.


Midvault Reconstruction in Primary Rhinoplasty.
The nasal midvault is an important consideration in rhinoplasty. This region is defined by the attachment of the upper lateral cartilages (ULCs) to the nasal bones superiorly and the cartilaginous septum medially. Inadequate management of the nasal midvault can have negative functional and aesthetic ramifications. Indications for midvault reconstruction in primary rhinoplasty include a narrow midvault, dorsal hump resection, a deviated midvault, and an asymmetric midvault, with an additional relative indication of zone 1 lateral wall insufficiency (LWI), defined as dynamic collapse of a weakened lateral nasal wall at the level of the ULC. Numerous techniques for midvault reconstruction have been described, dating back to Sheen's description of the spreader graft in the 1980s, which remains the gold standard for repair. Herein, the various indications for midvault reconstruction are described, along with a discussion of the most commonly used techniques for successful reconstruction.


The changes of angiogenesis and immune cell infiltration in the intra- and peri-tumoral melanoma microenvironment.
Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups--pT1 (35), pT2 (17), pT3 (18) and pT4 (12)--and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.


[Mesenteric lymph nodes in the rat after exposure to hydrocortisone].
The construction and cell composition of the cortex and medulla have been morphometrically studied after 1-, 3-, 5-, 7- and 14-aliquot injection of medical doses of hydrocortisone (0.25 mg per 100 g of body mass). The body mass of the animals decreases, as does the size of the mesenteric lymph nodes. The lymphocyto- and immunocytopoietic functions intensify in the medullary cords with a simultaneous inhibition of these processes in the cortical plateau and in the lymphoid noduli. On the 5th and 7th days there is some increase in the section area of the cortex, while that of the medulla decreases. The part of small lymphocytes in these structures grows large. Therefore, it is possible to suppose a definite tendency towards restoration of the structural components within two weeks.


Impaired Recent Verbal Memory in Pornography-Addicted Juvenile Subjects.
We aimed to find the differences in memory capabilities between pornography-addicted and nonaddicted juveniles. We enrolled 30 juveniles (12-16 y) consisting of 15 pornography addiction and 15 nonaddiction subjects. We used Rey Auditory Verbal Learning Test (RAVLT) to measure verbal memory, Rey-Osterrieth Complex Figure Test (ROCFT) for visual memory, along with Trail Making Test A and B (TMT-A and TMT-B) for attention. We found a significant reduction in the RAVLT A6 result of the addiction group (nonaddiction vs addiction: 13.47 ± 2.00 vs 11.67 ± 2.44, MD = -1.80, p=0.04), but not in ROCFT or attention tests. Analysis in sex subgroups yielded no sex-specific difference. We concluded that pornography addiction may be associated with impaired recent verbal memory in juveniles, regardless of sex and without association to attention.


Hypothyroid state does not protect but delays neuronal death in the hippocampal CA1 region following transient cerebral ischemia: focus on oxidative stress and gliosis.
We investigated protective effects of hypothyroidism on delayed neuronal death, gliosis, lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) in the gerbil hippocampal CA1 region (CA1) after 5 min of transient cerebral ischemia. The hypothyroidism was induced by 0.025% methimazole treatment. Free triiodothyronine and thyroxine levels were markedly decreased in the hypothyroid group. Four days after ischemia/reperfusion, only a few NeuN-immunoreactive (+) neurons were detected in the CA1 of euthyroid-ischemia (eu-ischemia) group; however, at this time point, the number of NeuN(+) neurons was significantly higher in the hypothyroid-ischemia (hypo-ischemia) group than in the eu-ischemia group. At 5 days postischemia, NeuN(+) neurons were significantly decreased in the hypo-ischemia group: The number of NeuN(+) neurons in this group was similar to that in the eu-ischemia group. Activations of GFAP(+) astrocytes and Iba-1(+) microglia in the CA1 were higher in the eu-ischemia group 3 and 4 days after ischemia/reperfusion. At 5 days postischemia, the activations of both the glial cells in the CA1 were similar between the two groups. 4-Hydroxy-2-nonenal (HNE), a marker for lipid peroxidation, immunoreactivity in the eu-ischemia group was higher than in the hypo-ischemia group; at 5 days postischemia, the immunoreactivity was similar between the two groups. In contrast, SOD1 level was lower in the CA1 of the eu-ischemia group. These results suggest that hypothyroid state does not protect against delayed neuronal death but only delays the neuronal death in the hippocampal CA1 region after transient cerebral ischemia by reducing lipid peroxidation and increasing SOD1.


Self-Generation in the Context of Inquiry-Based Learning.
Self-generation of knowledge can activate deeper cognitive processing and improve long-term retention compared to the passive reception of information. It plays a distinctive role within the concept of inquiry-based learning, which is an activity-oriented, student-centered collaborative learning approach in which students become actively involved in knowledge construction by following an idealized hypothetico-deductive method. This approach allows students to not only acquire content knowledge, but also an understanding of investigative procedures/inquiry skills - in particular the control-of-variables strategy (CVS). From the perspective of cognitive load theory, generating answers and solutions during inquiry-based learning is inefficient as it imposes an intrinsic and extraneous load on learners. Previous research on self-generation of content knowledge in inquiry-based learning has demonstrated that (1) a high cognitive load impairs retention of the generated information, (2) feedback is a fundamental requirement for self-generation of complex content knowledge, (3) self-generation success is key to long-term retention, and (4) generating and rereading place different demands on learners. However, there is still no research on the self-generation of scientific reasoning skills (procedural knowledge) and no knowledge of interaction between the (long-term) retention of these skills with prior knowledge, feedback and self-generation success. That is why this experiment was conducted. The focus of this research is to analyze the distinctive role of self-generation of scientific reasoning skills within the concept of inquiry-based learning and to identify the influence of prior knowledge and self-generation success on short-term and long-term retention. For this purpose, an experiment involving 133 6th and 7th graders was conducted. An inquiry activity that included the self-generation of scientific reasoning skills was compared to an inquiry task that had students simply read information about the experimental design. We used both an immediate and a delayed test to examine which treatment better developed a deeper understanding of CVS and an ability to apply this knowledge to novel problems (transfer). Direct instruction was clearly superior to self-generation in facilitating students' acquisition of CVS immediately after the inquiry task. However, after a period of 1 week had elapsed, both treatment conditions turned out to be equally effective. A generation effect was only found among students with high self-generation success after a 1-week delay.


Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth.
Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.


Designing individually randomized group treatment trials with repeated outcome measurements using generalized estimating equations.
Individually randomized group treatment (IRGT) trials, in which the clustering of outcome is induced by group-based treatment delivery, are increasingly popular in public health research. IRGT trials frequently incorporate longitudinal measurements, of which the proper sample size calculations should account for correlation structures reflecting both the treatment-induced clustering and repeated outcome measurements. Given the relatively sparse literature on designing longitudinal IRGT trials, we propose sample size procedures for continuous and binary outcomes based on the generalized estimating equations approach, employing the block exchangeable correlation structures with different correlation parameters for the treatment arm and for the control arm, and surveying five marginal mean models with different assumptions of time effect: no-time constant treatment effect, linear-time constant treatment effect, categorical-time constant treatment effect, linear time by treatment interaction, and categorical time by treatment interaction. Closed-form sample size formulas are derived for continuous outcomes, which depends on the eigenvalues of the correlation matrices; detailed numerical sample size procedures are proposed for binary outcomes. Through simulations, we demonstrate that the empirical power agrees well with the predicted power, for as few as eight groups formed in the treatment arm, when data are analyzed using the matrix-adjusted estimating equations for the correlation parameters with a bias-corrected sandwich variance estimator.