Novel agents for the treatment of alopecia.
Recent approval in the United States of two new products, Propecia (Merck Co, Rahway, NJ) and Rogaine Extra Strength 5% (Pharmacia & UpJohn Co, Kalamazoo, MI), indicated in men to promote scalp hair growth, have added a new dimension to treatment options offered by physicians in treating androgenetic alopecia (AGA). The search for new and effective agents to treat many different hair loss problems has been intensified by the increase in hair biology research taking place worldwide, from university academic institutions to the pharmaceutical companies. All have a desire to profit from marketing such drugs that have been termed, "cosmeceuticals". Millions of men and women of every race suffer from various forms of alopecia, the most common being AGA where the target tissue active androgen, 5 alpha-dihydrotestosterone (DHT) aggravates genetically programmed scalp hair follicles that results in short, fine, miniaturized hairs. Currently available to treat alopecia are drugs indicated for other disease processes because no other agents are accessible; some have severe side-effects and many are minimally effective. These prescription drugs were not originally indicated for alopecia and have not been adequately tested in controlled clinical trials to assess for efficacy, safety, and toxicity. These agents continue to be used clinically to treat patients with various forms of alopecia. As a result, a variety of new agents are emerging in the patient application process to gain protection and approval specifically for various forms of alopecia. This report reviews the most recently approved products, some of the more promising compounds in clinical trial development, as well as those in the over-the-counter (OTC) "natural" treatments category.


Fuzzy species borders of glacial survivalists in the Carpathian biodiversity hotspot revealed using a multimarker approach.
The Carpathians are one of the key biodiversity hotspots in Europe. The mountain chain uplifted during Alpine orogenesis and is characterised by a complex geological history. Its current biodiversity was highly influenced by Pleistocene glaciations. The goal of the current study was to examine the phylogenetic and demographic history of Gammarus balcanicus species complex in the Carpathians using multiple markers as well as to delimit, using an integrative approach, and describe new species hidden so far under the name G. balcanicus. Results showed that divergence of the studied lineages reaches back to the Miocene, which supports the hypothesis of their survival in multiple micro refugia. Moreover, the increase of their diversification rate in the Pleistocene suggests that glaciation was the driving force of their speciation. The climatic changes during and after the Pleistocene also played a major role in the demography of the local Carpathian lineages. Comparison of diversity patterns and phylogenetic relationships of both, the mitochondrial and nuclear markers, provide evidence of putative hybridisation and retention of ancient polymorphism (i.e., incomplete lineage sorting). The morphological examination supported the existence of two morphological types; one we describe as a G. stasiuki sp. nov. and another we redescribe as a G. tatrensis (S. Karaman, 1931).


Cooperative action of 1alpha,25-dihydroxyvitamin D3 and retinoic acid in NB4 acute promyelocytic leukemia cell differentiation is transcriptionally controlled.
All-trans-retinoic acid (RA) and 1alpha,25-dihydroxyvitamin D3 (1,25D3) are involved in the control of hematopoiesis and have been suggested to play a role in cellular differentiation and are as such potent inducers of differentiation of myeloid leukemia cells. In this study, we show that, in promyelocytic NB4 cells, addition of 1,25D3 enhances terminal granulocytic RA-dependent differentiation concomitant with the enhanced activation of the RA transcriptional activity through an RARbeta promoter. By EMSA and ChIP assays, we further demonstrate that, while both VDR and RAR are bound to the RARbeta promoter in NB4 cells, addition of 1,25D3 increases VDR binding to this promoter, while that of RA induces the release of VDR and increases the binding of RAR. Thus, contrary to normal myeloid cells, 1,25D3 does not act as a transrepressor of RA transcriptional activity in leukemic cells, suggesting that transcriptional regulation of RA-target genes may be modified in malignant cells. In promyelocytic leukemic cells, the combination of 1,25D3 and RA results in both enhanced transactivation and differentiation.


Extraosseous benign notochordal cell tumor presenting as bilateral pulmonary nodules.
Intraosseous benign notochordal cell tumors are rare and the likely precursors of chordoma. Extraosseous benign notochordal cell tumors have been reported in only 2 patients, and both presented as solitary pulmonary nodules. Here, we report a 53-year-old woman with an incidental finding of small nodules bilaterally in the lungs. The clinician suggested the tumors were metastases; however, histologic examination of both tumors showed benign notochordal cell tumor, characterized by adipocyte-like vacuolated cells with bland nuclei and lacking an intercellular myxoid matrix. Although extraosseous benign notochordal cell tumors are extremely rare, the diagnosis should be recognized by pathologists to avoid overtreatment of patients.


Stent graft-induced new entry tear after endoluminal grafting for aortic dissection repaired with open interposition graft.
Thoracic endovascular aortic repair is a successful treatment strategy for type B aortic dissections, with low morbidity and mortality compared with the gold standard of open repair. Questions still remain regarding its long-term durability and complication rate. There is a growing awareness of new entry tears induced by the stent graft, a potentially lethal complication. We report the case of a 74-year-old woman with a complicated retrograde type A aortic dissection treated with endovascular stent graft coverage. She required open surgical conversion after she developed a symptomatic, new entry tear induced by the stent graft.


[Physico-chemical properties of intra- and extracellular milieus at low temperatures. Influence of non-electrolytes].
The living activity of cells at freezing is determined by the peculiarities of physico-chemical properties of the medium. The effect of various biologically important molecules is determined by the ratio between polar and non-polar groups, by the structure of molecules. Structuration of the media contributes to the stabilization of cells. Optimization of the media content can change the cryohydrate temperature and living activity of the cells at given freezing conditions.


Clonal variation in the sensitivity of B16 melanoma to m-AMSA.
A hypothesis that m-AMSA may have greater cytotoxicity in melanin-containing tumour tissues, because it may reversibly bind to melanin, leading to prolonged drug exposure, was examined. Clonal lines of B16 melanoma which differed widely in pigmentation level were selected by isolating artificial lung colonies and in vitro soft-agar colonies, and implanting them into mice. Excision cell-survival assays performed 24 h after drug administration showed that in vivo sensitivity to m-AMSA progressively increased as pigmentation level decreased, but that m-AMSA drug levels measured 24 h after treatment were much lower in amelanotic than in melanotic lines. In dose-survival studies the reduced sensitivity of melanotic cell lines was revealed as a large shoulder (Dq = 27 mg/kg) though the terminal slopes for melanotic and amelanotic cell lines were similar (D10 approximately 31 mg/kg). Time-course studies indicated that there was no significant loss of drug from a melanotic cell line for 72 h after drug administration, though in an amelanotic cell line drug levels fell 10-fold in 10 h. There was, however, no evidence for prolonged drug cytotoxicity in the melanotic cell line. Using a fractionated drug-treatment regime, the greater cytotoxicity of m-AMSA to amelanotic tumour tissue was confirmed in a non-invasive regrowth-delay assay.


Lateralizing and localizing value of seizure semiology: Comparison with scalp EEG, MRI and PET in patients successfully treated with resective epilepsy surgery.
To evaluate the lateralizing and localizing value of seizure semiology in patients who became completely seizure free after resective epilepsy surgery. We analyzed seizures of patients who were seizure free after focal resection limited to the temporal lobe (30 patients), frontal lobe (27 patients), parietal lobe (8 patients) and occipital lobe (8 patients). Three investigators independently analyzed video segments of seizures blinded to clinical information and attempted to lateralize and localize the seizure focus, based on pre-defined criteria. Inter-observer agreement measured and positive predictive value were calculated and compared with scalp interictal, ictal EEG, MRI and PET. Seizure semiology correctly lateralized 19/30 (63%) temporal lobe epilepsy patients (kappa = 0.64); lobar localization was correct in 27/30 patients (90%) (Kappa = 0.6). Twenty of 27 (74%) frontal lobe patients were correctly lateralized (kappa = 0.55) and localized (Kappa = 0.41). Seven of 8 (87%) of parietal lobe patients were correctly lateralized (kappa = 0.83) and lobar localization was correct in 3/8 patients (37%) (Kappa = 0.5). Seven of 8 (87%) occipital lobe patients were correctly lateralized (kappa = 0.67) and lobar localization was correct in 7/8 patients (87%) (Kappa = 0.67). Collectively, seizure semiology was correctly lateralizing in 74% and correctly localizing in 77% of patients. Lateralization in secondarily generalized seizures was significantly higher compared to seizures that did not generalize (p = 0.0001). In non-lesional patients, lateralization was correct in 81% while localization was correct in 88% of patients. Seizure semiology has high lateralizing and localizing value, on par with interictal/ictal scalp EEG and MRI.


Maternal low molecular weight heparin versus sildenafil citrate for fetal growth restriction: a randomized, parallel groups, open-label clinical trial.
To compare the effect of sildenafil citrate (SC) and low molecular weight heparin (LMWH) on neonatal birth weight (BW) and the fetoplacental blood flow in pregnancies with FGR. A parallel groups, randomized clinical trial was conducted at a university hospital, between June 2017 and September 2018, involving 100 pregnant women with placental mediated FGR between 28 and 35 weeks of gestation who were randomly assigned to receive either SC or LMWH started at FGR diagnosis till delivery. The neonatal BW in LMWH group was higher than SC group (p < 0.000) with a longer time from randomization till delivery, LMWH group had significant improvement in Ut A PI, UA PI, and MCA PI compared with SC treated group with p values 0.005, <0.000001, and 0.014, respectively. The neonatal BW, time from randomization to delivery, and fetoplacental blood flow indices were significantly better with LMWH use compared with SC.


Acidosis inhibits spontaneous activity and membrane currents in myocytes isolated from the rabbit atrioventricular node.
Recent evidence from intact hearts suggests that the function of cardiac nodal tissue may be particularly susceptible to acidosis. Little is currently known, however, about the effects of acidosis on the cellular electrophysiology of the atrioventricular node (AVN). This study was conducted, therefore, to determine the effect of acidosis on the spontaneous activity and membrane currents of myocytes isolated from the rabbit AVN, recorded at 35-37 degrees C using whole-cell patch-clamp. Reduction of extracellular pH (pH(e); from 7.4 to 6.8 or 6.3) produced pH-dependent slowing of spontaneous action potential rate and upstroke velocity, and reductions in maximum diastolic potential and action potential amplitude. Ionic current recordings under voltage-clamp indicated that acidosis (pH(e) 6.3) decreased L-type Ca current (I(Ca,L)), without significant changes in voltage-dependent activation or inactivation. Acidosis reduced the E-4031-sensitive, rapid delayed rectifier current (I(Kr)) tail amplitude at -40 mV following command pulses to between -30 and +50 mV, and accelerated tail-current deactivation. In contrast, the time-dependent hyperpolarisation-activated current, I(f), was unaffected by acidosis. Background current insensitive to E-4031 and nifedipine was reduced by acidosis. Measurement of intracellular pH (pH(i)) from undialysed cells using BCECF showed a reduction in mean pH(i) from 7.24 to 6.45 (n=17) when pH(e) was lowered from 7.4 to 6.3. We conclude that I(f) is unlikely to be involved in the response of the AVN to acidosis, whilst inhibition of I(Ca,L) and I(Kr) by acidosis are likely to play a significant role in effects on AVN cellular electrophysiology.


Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes.
The antibody responses to a novel rapid-acting insulin analog, insulin aspart (IAsp), and their potential clinical correlates were studied with a specifically developed method in 2,420 people with diabetes treated for up to 1 year with preprandial subcutaneous injections of IAsp. Circulating insulin antibodies were analyzed by radioimmunoassay with (125)I insulin or IAsp tracers and polyethylene glycol precipitation. Four multinational, open, parallel group studies were conducted in Europe and North America, with a total of 1,534 people with diabetes exposed to IAsp and 886 people exposed to human insulin (HI) as meal-related insulin for 6-12 months. Insulin antibodies specific to HI or IAsp were absent in a majority of patients throughout the 6- to 12-month study periods. A majority of the patients (64-68%) had antibodies cross-reacting between HI and IAsp when entering the studies, with baseline levels (means +/- SD of percent bound/total) of 16.6 +/- 16.3% in study 1 and 10.3 +/- 14.0% in study 4. In all four studies, cross-reactive antibodies increased in patients exposed to IAsp, with a maximum at 3 months, and thereafter there was a decline toward baseline levels at 9-12 months (levels at 3 and 12 months: 22.3 +/- 19.7 and 16.8 +/- 16.5% in study 1 and 21.5 +/- 21.9 and 16.9 +/- 17.4% in study 4). Antibody levels showed similar changes in people with type 1 and type 2 diabetes, and there was no consistent relationship between antibody formation and glycemic control or between antibody formation and safety in terms of adverse events. Treatment with IAsp is associated with an increase in cross-reactive insulin antibodies, with a subsequent fall toward baseline values, without any indication of clinical relevance because no effect on efficacy or safety could be identified.


BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer.
While the role of BRCA1/2 genes in familial breast and ovarian cancer is well established, their implication in the sporadic form of both cancers is still controversial. With the development of poly (ADP-ribose) polymerase (PARP) inhibitors, the exact relationship between BRCA1/2 genes and sporadic triple negative breast cancer/high grade serous carcinoma (TNBC/HGSC) needs to be further investigated. Therefore, we conducted a study in which we analyze BRCA1/2 point mutations and copy number alterations in Moroccan patients suffering from TNBC/HGSC. To achieve our goal, we analyzed BRCA1/2 genes in the FFPE tissue blocks and blood samples of 65 TNBC/HGSC selected patients, using next generation sequencing technology. From the 65 successfully sequenced patients in our cohort, we detected five-point variants in six different patients, four variants were classified as pathogenic and one of unknown significance. Regarding copy number alterations we detected one copy number loss in BRCA1 gene and one copy number gain in BRCA2 gene. The genetic screening of BRCA1/2 genes using these patients' genomic DNA indicated that five harbored a germline genetic alteration. While three harbored a somatic genetic alteration. To the best of our knowledge, three-point variants detected in our study have never been reported before. According to the results found in the present study, in a population without a family history of cancer, the possibility of a BRCA1/2 somatic pathogenic variant in high grade serous carcinoma is 7%. While for Triple negative breast cancer somatic point variants and copy number alterations seems to be a very rare genetic event.


Doppler echocardiography in cardiac tamponade: exaggerated respiratory variation in transvalvular blood flow velocity integrals.
Pulsed Doppler echocardiography has been used previously to demonstrate marked changes in transvalvular blood flow velocities during cardiac tamponade in laboratory animals and a small number of patients. To further assess the respiratory changes in transvalvular blood flow during tamponade, pulsed Doppler tracings of flow velocity profiles across all four cardiac valves were recorded during inspiration and expiration in 13 patients during cardiac tamponade, in 6 of the 13 patients after relief of tamponade by pericardiocentesis and in 8 normal control subjects. Flow velocity integrals were calculated for each valve during inspiration and expiration. In the setting of cardiac tamponade, inspiration caused an 85 +/- 46% increase in the flow velocity integral across the pulmonary valve, an 81 +/- 34% increase across the tricuspid valve, a 33 +/- 13% decrease across the aortic valve and a 35 +/- 8% decrease across the mitral valve. These phasic respiratory changes were markedly reduced after relief of tamponade (p less than 0.05 compared with tamponade) and were observed to only a minimal extent in the normal individuals (p less than 0.01 compared with tamponade). The exaggerated respiratory variations in transvalvular flow velocity integrals suggest that Doppler evaluation may be a valuable tool in the diagnosis of cardiac tamponade. Transmitral Doppler indexes of left ventricular filling during cardiac tamponade revealed that inspiration caused a shift to increased filling during late diastole, with a greater contribution of atrial systole to total left ventricular filling. These Doppler indexes did not vary significantly with respiration in the group studied after relief of tamponade or in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


Adalimumab Therapeutic Drug Monitoring Improves Treatment Outcome in Patients with Psoriasis.
Therapeutic drug monitoring (TDM) or the measurement of drug concentrations (ideally at trough level) and antidrug antibodies are important tools for optimizing biologic therapy. Limited studies evaluated TDM in dermatological indications. A retrospective study of 170 patients with psoriasis who were treated with adalimumab and received TDM reported that adalimumab TDM is practical and promising in routine psoriasis care. However, TDM interpretation requires careful attention to the clinical context to address the controversies and challenges.


HEMORRHAGIC RISK OF VITREORETINAL SURGERY IN PATIENTS MAINTAINED ON NOVEL ORAL ANTICOAGULANT THERAPY.
To evaluate the frequency and type of perioperative hemorrhagic complications associated with vitreoretinal surgery in patients undergoing systemic treatment with the newer anticoagulant and antiplatelet agents including rivaroxaban, apixaban, dabigatran, and prasugrel. Retrospective review of a cohort of patients being treated with anticoagulant and antiplatelet drugs, who underwent any vitreoretinal surgical procedure over a 2-year period. Thirty-six eyes of 33 patients were identified who underwent vitreoretinal surgical operations while being treated systemically with anticoagulant and antiplatelet therapy. No eyes suffered perioperative complications of retrobulbar hemorrhage, suprachoroidal hemorrhage, or subretinal hemorrhage. Four eyes (11.1%) experienced postoperative vitreous cavity hemorrhage after which two eyes (5.5%) required repeat surgical intervention and two eyes (5.5%) cleared spontaneously. Although there is a relative risk to such surgery in patients who are taking novel oral anticoagulants, these findings suggest that patients may safely undergo vitreoretinal surgery while maintaining therapy with rivaroxaban, apixaban, dabigatran, and prasugrel.


VeSpAR trial: a randomized controlled trial comparing vessel-sparing anastomotic repair and transecting anastomotic repair in isolated short bulbar urethral strictures.
Vessel-sparing anastomotic repair (vsAR) has been developed as a less traumatic alternative to transecting anastomotic repair (tAR) to treat isolated short bulbar urethral strictures. This vessel-sparing technique could result in improved functional outcomes without jeopardizing the excellent surgical outcome after (transecting) anastomotic repair. The purpose of this study is to directly compare vsAR and tAR for both surgical and functional outcomes. This trial is a prospective, interventional, multi-center, single-blinded, 1:1 randomized, controlled, non-inferiority, phase II trial. Sample size calculation resulted in a required sample size of 100 patients (50 patients per arm). Trial participants will be randomized by an independent third party using a computer-based random sequence generator with permuted blocks of variable size. The primary objective of this trial is to show that vsAR is non-inferior to tAR in terms of failure-free survival after 24 months of follow-up, considering a non-inferiority limit of 10%. Failure is defined as the inability to pass a 16-Fr flexible cystoscope through the reconstructed area without damaging the urethral mucosa. Secondary end-points mainly include differences in postoperative complications and changes in functional outcome parameters, which will be assessed with validated questionnaires. All participants are scheduled for follow-up at 3, 12, and 24 months postoperatively. This trial will provide level Ib evidence about the differences in both surgical and functional outcome between vsAR and tAR, which may importantly scape the future of bulbar urethral reconstruction. Depending on the trial results, this phase II trial may generate a larger phase III trial with more statistical power and a lower alpha value. This trial is registered at clinicaltrials.gov ( NCT03572348 ) and in the Belgian Clinical Trial Registry (B670201837335). The trial was registered prospectively. Registered on 28 June 2018.


Alanine scanning mutagenesis of anti-TRAP (AT) reveals residues involved in binding to TRAP.
The trp RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic (trp) genes in response to changes in intracellular levels of free l-tryptophan in many Gram-positive bacteria. When activated by binding tryptophan, TRAP binds to the mRNAs of several genes involved in tryptophan metabolism, and down-regulates transcription or translation of these genes. Anti-TRAP (AT) is an antagonist of TRAP that binds to tryptophan-activated TRAP and prevents it from binding to its RNA targets, and thereby up-regulates trp gene expression. The crystal structure shows that AT is a cone-shaped trimer (AT(3)) with the N-terminal residues of the three subunits assembled at the apex of the cone and that these trimers can further assemble into a dodecameric (AT(12)) structure. Using alanine-scanning mutagenesis we found four residues, all located on the "top" region of AT(3), that are essential for binding to TRAP. Fluorescent labeling experiments further suggest that the top region of AT is in close juxtaposition to TRAP in the AT-TRAP complex. In vivo studies confirmed the importance of these residues on the top of AT in regulating TRAP mediated gene regulation.


Stress fracture of the ulna in an adolescent baton twirler.
Upper extremity stress fractures are rare, with the majority of those reported occurring in the ulna. The location of the fracture is influenced by the type of activity and mechanism of injury with which it is associated. We report the first case of a mid-ulnar stress fracture in a baton twirler due to chronic torsional stress. This patient was referred to our Orthopedic Oncology clinic with a preliminary diagnosis of osteoid osteoma.


Evaluation of screening tools for dementia in older adults with mental retardation.
We compared groups with and without diagnosed dementia matched on IQ, age, and presence of Down syndrome. The Dementia Scale for Down Syndrome and Dementia Questionnaire for Mentally Retarded Persons were used to assess participants. We developed two performance tasks to determine whether they were useful in separating subjects with and without dementia and also used the Reiss Screen. Both dementia scales and both performance tasks discriminated between groups. The dementia scales were not related to premorbid IQ, age, or gender, whereas performance tasks were related to dementia and IQ but not age or gender. Various Reiss Screen subscales also discriminated between groups. Subscales of the screening instruments and performance tasks were significantly related, indicating congruent validity. Logistic regression was conducted to assess which combination of tests discriminated best between groups.


Susceptibility of endodontic pathogens to antibiotics in patients with symptomatic apical periodontitis.
The aim of this study was to evaluate susceptibility of predominant endodontic pathogens isolated from teeth with symptomatic apical periodontitis to most commonly prescribed antibiotics. Among 58 patients with symptomatic apical periodontitis, 47 and 11 cases were caused by primary and secondary root canal infection, respectively. The microbial samples were taken either from the root canals (35 cases) or by aspiration from apical abscesses (23 cases). Culture methods were used to identify the microorganisms present in the samples. Antibiotic susceptibilities of all isolates were evaluated by using the E-test method. Microorganisms were isolated from 49 of the 58 samples studied and included facultative and obligate anaerobes. Streptococci and obligate anaerobes were the predominant microorganisms in cases of primary infection. Enterococcus faecalis dominated in cases of secondary infection. All tested microorganisms were highly sensitive to penicillin G, amoxicillin, and ampicillin. Susceptibilities to clindamycin and erythromycin were 73.8% and 54.7%, respectively. About 40% of the isolates were resistant to tetracycline. More than 50% of all anaerobes were resistant to metronidazole. All E. faecalis isolates were resistant to clindamycin. Based on the study results, penicillin and amoxicillin are suitable antibiotics for treatment of endodontic infection when conventional root canal treatment alone is insufficient. Clindamycin could be advised for penicillin-allergic patients with primary endodontic infections.


Rising prevalence, and improved but suboptimal management, of hypertension in South Africa: A comparison of two national surveys.
To examine the changes in prevalence, awareness, treatment and control of hypertension between 1998 and 2016 in ≥15-year-old South African men and women and the sociodemographic characteristics associated with those changes. In nationally representative surveys in 1998 and 2016, multi-stage sampling was used to select, interview and collect blood pressure and anthropometric measurements in ≥15-year-old adults. Logistic regression analyses evaluated the independent effects of selected sociodemographic characteristics on hypertension management. Among 13,217 participants in 1998 and 7830 in 2016 (59-60% women in both surveys), hypertension prevalence increased from 27% to 45% in men and 31% to 48% in women. Hypertension increased equally in participants with and without obesity and in daily cigarette smokers vs. their counterparts. Prevalence of awareness among participants with hypertension increased from 7% to 18% (men) and from 17% to 29% (women). Among those aware, hypertension treatment improved markedly from 8% to 85% (men) and from 12% to 82% (women). Hypertension control among those on treatment increased from 17% to 26% (men) and from 21% to 30% (women). Increasing age and survey year were consistently associated with higher prevalence, awareness, treatment and control of hypertension. The richest vs. poorer women, and lower vs. higher educated women were more likely to be treated for hypertension. The high and rising hypertension burden together with suboptimal awareness and control levels warrant greater attention to curb hypertension-related morbidity and mortality in South Africans. Novel strategies involving community-based or workplace hypertension programmes may overcome some barriers to optimal care.


IGM-containing immune complexes and antiphospholipid antibodies in patients with Sneddon's syndrome.
We report three patients with a Sneddon syndrome in whom predominantly small (500-900 kD) IgM-containing serum immune complexes were detectable. Furthermore, antiphospholipid antibodies and increased von Willebrand factor antigen were found in the sera of two cases. Especially the data demonstrating small circulating immune complex as suggest that Sneddon's syndrome, a rare vasculitis disorder, might immunologically be characterized by circulating IgM-containing immune complexes which, in addition, could play a role in the pathogenesis of this disease entity. The elevated antiphospholipid antibodies as well as the increased von Willebrand factor antigen in the sera of the investigated patients have to be considered as nonspecific vasculitis-associated phenomena.


The Barrow Neurological Institute screen for higher cerebral functions in cognitive screening after stroke.
The objective of this study was to evaluate the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) in screening for cognitive dysfunction at long-term follow-up after stroke in young and middle-aged patients. Within the Sahlgrenska Academy Study on Ischemic Stroke Outcome, the BNIS and the Mini-Mental State Examination (MMSE) were administered to 295 consecutive surviving patients seven years after ischemic stroke. All participants were less than 70 years at index stroke. BNIS score less than 47 and an MMSE score less than 29 were chosen to indicate cognitive dysfunction. Two hundred eighty-one (95%) patients completed both tests. The 2 test scores were moderately correlated, and both tests correlated to disability as measured by the modified Rankin Scale. The distribution of the MMSE score was skewed toward the top scores, with a marked ceiling effect, whereas the BNIS score was more normally distributed. Most BNIS subscales showed mean performance around the mid of the scale without ceiling effects. Both tests identified a large proportion of the subjects as cognitive impaired, however, with a substantially larger proportion for the BNIS (89%) compared with the MMSE (65%). We conclude that the BNIS may be a useful screening instrument for cognitive dysfunction after ischemic stroke and that a large proportion of young and middle-aged ischemic stroke survivors showed signs of cognitive dysfunction long after index stroke. Further validations of BNIS against formal neuropsychological testing and studies of the determinants and consequences of long-term cognitive outcome in this patient group are warranted.


Evaluating DNA sequence variants of unknown biological significance.
Increasingly, the molecular genetics laboratory has to assess the biological significance of changes (variants) in a DNA sequence. Using the large genes BRCA1 and BRCA2 as examples, some approaches used to determine the biological significance of DNA variants are described. These include the characterization of the variant through a review of the literature and the various databases to assess if it has previously been described. Potential difficulties with the various databases that are available are described. Other considerations include the co-inheritance of the variant with other DNA changes, and its evolutionary conservation. Determining the possible effect of the variant on protein function is described in terms of the Grantham assessment as well as identifying functional domains. Studies looking at the distribution of the variant in both the population and the family can also help in assessing its significance. Loss of the variant in a tumor sample would imply that it is not deleterious. Ultimately, it is not any single parameter that helps determine the DNA variants biological significance. Usually this requires multiple lines of evidence.


The Effect of Endophytic Talaromyces pinophilus on Growth, Absorption and Accumulation of Heavy Metals of Triticum aestivum Grown on Sandy Soil Amended by Sewage Sludge.
Sewage sludge improves agricultural soil and plant growth, but there are risks associated with its use, including high heavy metal content. In this study, experiments were carried out to investigate the role of endophytic Talaromyces pinophilus MW695526 on the growth of Triticum aestivum cultivated in soil amended with sewage sludge and its phytoremediation ability. T. pinophilus could produce gibberellic acid (GA) and stimulate T. aestivum to accumulate GA. The results showed that inoculation with T. pinophilus boosted plant growth criteria, photosynthetic pigments, osmolytes (soluble proteins, soluble sugars and total amino acids), enzymatic antioxidants (catalase, superoxide dismutase and peroxidase), K, Ca and Mg. On the other hand, it reduced Na, Na/K ratio, Cd, Ni, Cu and Zn in the growth media as well as in the shoot and root of T. aestivum. The results suggest that endophytic T. pinophilus can work as a barrier to reduce the absorption of heavy metals in T. aestivum cultivated in soil amended with sewage sludge.


Novel angucycline compound with both antigastrin- and gastric mucosal protective-activities.
An angucycline series compound P371 A1 (1) from Streptomyces sp. P371 was established to have a novel structure comprising an ureido group at one of four sugar units on the basis of 2D NMR techniques. 1 exhibited an inhibitory activity against the pentagastrin-stimulated acid secretion as well as protective activities against HCl/ethanol- and indomethacin-induced gastric lesions.


[Evolution of the yeast microflora during the first days of fermentation in inoculated Majorcan musts].
Three fermentations were carried out with grape must of the Callet variety. This cultivar is considered autochthonous from the island of Majorca. Two tanks were inoculated with starting cultures of selected yeasts and the last was fermented spontaneously by wild yeasts. The frequency of yeast isolates during the early stages of the fermentation, showed that Candida stellata was more affected by the inoculation than the other wild yeasts with the exception of Saccharomyces cerevisiae. The chemical analyses of wines showed a better alcoholic rate and less volatile acidity in the inoculated wines. Two sensorial analyses were performed and significant differences between the wines were noted.


[Supraciliary microstent for open-angle glaucoma: clinical results of a prospective multicenter study].
The suprachoroidal CyPass micro-stent is designed to be implanted into the supraciliary space to facilitate aqueous outflow along the uveoscleral pathway in patients with open-angle glaucoma (OAG). This study assessed the safety of micro-stent implantation in patients undergoing cataract surgery. In this multicenter study the CyPass microstent was implanted in patients with OAG undergoing cataract surgery. The implantation was performed using a minimally invasive, conjunctiva-sparing, ab interno intervention. Primary endpoints were safety aspects of the implant, secondary endpoints were the reduction of intraocular pressure (IOP) and topical medication. There were no severe adverse events during or after surgery in any of the patients. In patients with controlled glaucoma (IOP < 21 mmHg) the average IOP remained constant throughout the 24 month follow-up period but mean medication use decreased from 2.0 at baseline to 1.1 postoperative. In patients with IOP of ≥ 21 mmHg the pressure was reduced by 37 % postoperatively and mean medication decreased from 2.2 at baseline to 1.0. The safety profile of combined cataract surgery and CyPass microstent implantation is acceptable and patients also showed a decrease in IOP and medication use.


Quantitative determination of pyloric regurgitation in response to intraduodenal bolus injection.
Employing 99m Tc-colloid and external scanning, a test has been developed to measure duodeno-gastric regurgitation quantitatively. The test is relatively simple and its reproducibility is good. Thirty-two patients with type I gastric ulcer had a median reflux of 14%, significantly higher than nine controls and nine duodenal ulcer patients with a median reflux of 4% and 5%, respectively.


Serial MRI scans help in assessing early response to neoadjuvant chemotherapy and tailoring breast cancer treatment.
Tailoring neoadjuvant chemotherapy (NAC) during breast cancer treatment is performed to improve overall tumour response, with increasing evidence to support its role. This study evaluates our breast unit's experience in MRI assessment of tumour response as an aid in tailoring NAC. This is a retrospective study of patients treated with NAC for breast cancer between 2005 and 2009 who underwent MRI to assess tumour response. Response to NAC was monitored before NAC and after 2 and/or 4 cycles of anthracycline and cyclophosphamide (AC) chemotherapy. Taxane was substituted for AC if MRI response was deemed inadequate. Tumour response on last MRI was correlated with final pathology against different tumour subtypes and in inflammatory tumours. Strength of agreement was measured using Kappa analysis. Potential predictive factors for MRI response were assessed for significance. 166 tumours were assessed with serial MRI scans. MRI showed high sensitivity rate (93.1%) in predicting response to NAC particularly for tumours showing partial (PR) or complete (CR) response on pathology (p < 0.001) with fair agreement on Kappa analysis (K = 0.31). MRI seems more accurate in triple negative, HR+/HER2+ and high-grade tumours. Early identification of non-responders on MRI resulted in early tailoring of NAC, with improved rates of tumour response seen in 74.2% following switching NAC. Logistic regression showed that PR or CR observed on MRI after 2 NAC cycles significantly predicted pCR (p < 0.001). Serial MRI can be used to assess patterns of tumour response to NAC. This study shows that tailoring NAC according to pattern of response can improve overall tumour response rates.


Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis.
The indications for liver transplantation in cases of fulminant hepatitis are currently determined according to the Guideline of the Acute Liver Failure Study Group of Japan in 1996, which is based on assessment of the prognosis of the patients at the onset of hepatic encephalopathy and reassessed 5 days later. This Guideline was prepared based on the clinical findings in patients seen between 1988 and 1992, and showed a predictive accuracy of 82% in the patients seen between 1993 and 1995. In this study, the usefulness of the Guideline was re-evaluated, since the therapeutic strategies for fulminant hepatitis have advanced remarkably over the last 10 years. The predictive accuracy of the Guideline was assessed in 698 patients with fulminant hepatitis and late onset hepatic failure (LOHF) between 1998 and 2003. The time-point in the course of the disease at which physicians considered liver transplantation was examined. The accuracy in patients not receiving liver transplantation was 68% and 78% in acute and subacute types, respectively, of fulminant hepatitis, and 84% among LOHF cases. The values did not improve following the reassessment. The sensitivity and specificity of the assessment in patients with acute and subacute types, respectively, were extremely low. Liver transplantation was considered in 42% of LOHF patients at 8 or more days before encephalopathy development. The Guideline should be modified to improve its accuracy. The Guideline should also be made adoptable for the assessment of LOHF patients before hepatic encephalopathy onset.


Pontine cholinergic neurons depend on three neuroprotection systems to resist nitrosative stress.
Brainstem cholinergic populations survive in neurodegenerative disease, while basal forebrain cholinergic neurons degenerate. We have postulated that variable resistance to oxidative stress may in part explain this. Rat primary cultures were used to study the effects of several nitrosative/oxidative stressors on brainstem (upper pons, containing pedunculopontine and lateraldorsal tegmental nuclei; BS) cholinergic neurons, comparing them with medial septal (MS), and striatal cholinergic neurons. BS cholinergic neurons were significantly more resistant to S-nitro-N-acetyl-d,l-penicillamine (SNAP), sodium nitroprusside (SNP), and hydrogen peroxide than were MS cholinergic neurons, which in turn were more resistant than striatal cholinergic neurons. Pharmacological analyses using specific inhibitors of neuroprotective systems also revealed differences between these three cholinergic populations with respect to their vulnerability to SNAP. Toxicity of SNAP to BS neurons was exacerbated by blocking NF-kappaB activation with SN50 or ERK1/2 activation by PD98059, or by inhibition of phosphoinositide-3 kinase (PI3K) activity by LY294002. In contrast, SNAP toxicity to MS neurons was augmented only by SN50, and SNAP toxicity to striatal cholinergic neurons was not increased by any of these three pharmacological agents. In neuron-enriched primary cultures, BS cholinergic neurons remained resistant to SNAP while MS cholinergic neurons remained vulnerable to this agent. Immunohistochemical experiments demonstrated nitric oxide (NO)-induced increases in nuclear levels of phospho-epitopes for ERK1/2 and Akt, and of the p65 subunit of NF-kappaB, within BS cholinergic neurons. These data indicate that the relative resistance of BS cholinergic neurons to toxic levels of nitric oxide involves three intrinsic neuroprotective pathways that control transcriptional and anti-apoptotic cellular functions.


Heterologous expression of the chrysanthemum R2R3-MYB transcription factor CmMYB2 enhances drought and salinity tolerance, increases hypersensitivity to ABA and delays flowering in Arabidopsis thaliana.
Knowledge on genes related to plant responses to adverse growth conditions and development is essential for germplasm improvement. In this study, a chrysanthemum R2R3-MYB transcription factor gene, designated CmMYB2 (GenBank accession No. JF795918), was cloned and functionally characterized. Expression of CmMYB2 in chrysanthemum leaves was up-regulated in response to drought, salinity and cold stress, as well as by treatment with exogenous abscisic acid (ABA). When the gene was constitutively expressed in Arabidopsis thaliana, it increased plant sensitivity to ABA and reduced stomatal aperture. Plant survival under drought was improved than in the wild type, as was the plants' salinity tolerance. The level of expression of a number of genes associated with the stress response, including RD22, RD29A, RAB18, COR47, ABA1 and ABA2, was raised in the CmMYB2 transgenic Arabidopsis plants. CmMYB2 transgenic Arabidopsis plants were also delayed in flowering. The expression of CONSTANS (CO), FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1), LEAFY (LFY) and APETALA1 (AP1) genes involved in flowering was down-regulated in the CmMYB2 transgenics. Together, these results suggest that CmMYB2 may be a promising gene for the drought and salt tolerance improvement and flowering-time modulation.


Reduced Fhit expression in cervical carcinoma: correlation with tumor progression and poor prognosis.
The fragile histidine triad (FHIT) gene is located at chromosome 3p14.2 and encompasses the common fragile site, FRA3B, which may contribute to chromosome breakage and rearrangement of cancer cells. Aberrant protein expression and inactivation of the FHIT gene have been identified in a variety of precancerous and cancerous lesions. To identify the potential implications of the FHIT gene in the development of cervical carcinoma and explore the clinical importance of change in gene expression, we assessed the level of Fhit protein in precancerous lesions and carcinomas of the cervix. In our study, 15 low-grade squamous intraepithelial lesions (LSIL), 35 high-grade squamous intraepithelial lesions (HSIL), 12 microinvasive carcinomas, and 103 invasive carcinomas were evaluated. The expression of Fhit was studied by immunohistochemistry using a polyclonal antibody specific for the protein. All samples of normal epithelium and LSIL exhibited intermediate to strong immunostaining of Fhit. Reduced Fhit protein expression was observed in 30 of 103 (29.1%) invasive carcinomas, 1 of 12 (8.3%) microinvasive carcinomas, and 3 of 35 (8.6%) HISL. Compared with normal epithelium and dysplasia, microinvasive and invasive carcinomas showed significantly lower Fhit expression. Fhit expression was also correlated with clinicopathological status. Reduced Fhit expression was significantly associated with lymph node metastasis (P = 0.005), parametrial invasion (P = 0.023), and vaginal involvement of the tumor (P = 0.016). In univariate analysis, Fhit expression was found to be a significant predictor of survival (relative risk 2.54, P = 0.0091): the patient with reduced Fhit expression had a 154% higher risk of dying from cervical cancer than the patient with opposite values. Our results indicate that immunostaining of Fhit expression has potential as a prognostic marker in the management of cervical cancer. The trend of reduced Fhit expression in microinvasive and invasive carcinomas suggests that down-regulation of Fhit is strongly linked to cancer progression. Moreover, loss of Fhit expression was related to lymph node metastasis, parametrial invasion, and vaginal involvement in cervical carcinoma. These results imply that loss of Fhit protein is associated with highly aggressive phenotypes of cervical carcinoma.


Collagenous and lymphocytic colitis: subject review and therapeutic alternatives.
To review the published studies on collagenous and lymphocytic (microscopic) colitis with specific emphasis on clinical features, investigational studies, characteristic histology, possible pathogenesis, disease course, and empirical treatment. Comprehensive synopsis of the stated objective, prepared for the physician treating patients with collagenous or lymphocytic colitis. The medical literature on collagenous and lymphocytic colitis. Collagenous and lymphocytic colitis are chronic diarrheal illnesses of indeterminate etiology that typically present in the late sixth or early seventh decade of life. These disorders may be distinct entities, although some data support the idea that they are only different manifestations of the same disease. The pathogenesis is unknown but may be on an inflammatory, possibly autoimmune, basis. Physical examination and investigational studies are normal or nonspecific, with fecal leukocytosis the only abnormality found in the majority of patients tested. Association with various gastrointestinal, autoimmune, and rheumatologic conditions has been observed in some patients. Clinical and occasional histologic response has been observed after treatment with anti-inflammatory agents such as 5-aminosalicylate and corticosteroids, and should be used when there is no response to symptomatic therapy. Collagenous and lymphocytic colitis are uncommon but important causes of chronic diarrhea which are important to diagnose and treat.


Functional expression of arginine kinase improves recovery from pH stress of Escherichia coli.
Acid stress in Escherichia coli involves a complex resource- and energy-consuming response mechanism. By overexpression of arginine kinase from Limulus polyphemus in E. coli, we improved the recovery from a transient pH stress. While wild type E. coli resumed growth after a transient pH reduction to pH 3 for 1 h with a rate that was 25% lower than before the stress, the arginine kinase expressing strain continued to grow as rapidly as before. This effect is presumably caused by the physiological function of arginine kinase as a short term energy buffer in the form of phosphoarginine, but a pH-buffering effect cannot be excluded.


Contradictory functions of NF-kappaB in liver physiology and cancer.
Rudolf Virchow (1821-1902), one of the founding fathers of modern pathology, hypothesized that cancer and inflammatory processes are linked, due to the presence of leukocytes in the tumor tissue. Today, chronic inflammation is believed to be one of the major causes for cancer development, accounting for nearly 20% of cancer cases worldwide. Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality throughout the world, and its incidence is increasing in the United States. HCC is widely accepted to be the outcome of continuous injury and chronic inflammation, and thus provides a good model to gain insight into inflammatory related cancer processes. Nuclear Factor- kappa B (NF-kappaB) was first identified as an enhancer protein of the kappa light-chain gene in B lymphocytes. Later it was realized that there are five NF-kappaB transcription factors with important roles in inflammation, innate immunity, cancer and apoptosis aborting. Consequently, NF-kappaB was shown to link inflammation and cancer, but recent reports have revealed it to play a much more complex role, where in some disease processes it promotes cancer and in others it impedes carcinogenesis. In this review, we will focus on the seemingly contradictory role of NF-kappaB in liver homeostasis, as well as in liver cancer.


The behavior of fixed and switching oxide traps of RADFETs during irradiation up to high absorbed doses.
The behavior of radiation-induced fixed traps (FTs) in gate oxide and radiation-induced switching traps (STs) near and at the gate oxide/substrate interface during irradiation up to high absorbed doses has been considered. The zero-bias voltage regime, the simplest and most popular solution in practice, was chosen. Indeed, it is very difficult to predict the creation of radiation defects in the case of low electric fields, because there is a compromise between the external low electric fields induced by work function differences and the internal electrical fields induced by radiation-induced charged defects in the oxide. It was shown that the density of FTs is higher than the density of STs for lower absorbed doses, though the trend is reversed for doses greater than 700Gy. Although the number of FTs is much higher than the number of STs, many FTs are located in the bulk, far from the oxide/semiconductor interface and their influence on channel carriers is much smaller than the influence of STs that are located closer to the channel. The equation for fitting the threshold voltage components induced by FTs (ΔVft) and by STs (ΔVst) is proposed and very good fittings are obtained. It is shown that five experimental irradiation points are sufficient to draw a good conclusion about the values of the fitting parameters, i.e., the voltage saturation values and the degree of linearity.


Obstacles associated with organizational change.
This article briefly explores one view of the change process, discusses obstacles to change, the means to deal with these obstacles, and describes change principles and specific examples of change strategies that commonly work.


Ethnopharmacological nexus between the traditional Thai medicine theory and biologically based cancer treatment.
The two major theories utilized for diagnosis and treatment in Traditional Thai Medicine (TTM) are the Four Element Theory and the Herbal Flavor Theory. A TTM "Poh-Pu" Remedy has been effectively utilized in Thailand for cancer therapy for centuries. To investigate anti-inflammatory activity and liver cancer cytotoxicity of Poh-Pu remedy. To determine relationships between the TTM Herbal Flavor theory and the Four Element theory and total flavonoid content and biological activities of Poh-Pu Remedy plant extracts. Each plant ingredient was macerated with 95% ethanol. The extracts were investigated for cytotoxic activity against liver cancer using a sulforhodamine B assay, and anti-inflammatory activity was evaluated by inhibition of nitric oxide production. The total flavonoid content was determined by an aluminum chloride colorimetric assay. The relationships between the TTM theories, total flavonoid content, and biological activities were evaluated by correlation and cluster analysis. Mammea siamensis exerted potent cytotoxicity against hepatocellular carcinoma (HepG2) cell lines with an IC50 of 3.15 ± 0.16 μg/mL and low cytotoxicity to the non-cancerous cells (HaCat) with an IC50 33.39 ± 0.40 μg/mL (Selective index (SI) = 10.6). Tiliacora triandra was selectively cytotoxic to cholangiocarcinama (KKU-M156) cells with an IC50 of 12.65 ± 0.92 μg/mL (SI = 6.4). Curcuma comosa was the most potent anti-inflammatory inhibitor of nitric oxide production with an IC50 of 2.75 ± 0.34 μg/mL. Campomanesia aromatica exhibited the highest total flavonoid content of 259.7 ± 3.21 mg quercetin equivalent/g. Pungent plants were most prevalent in the TTM remedy. Pungent, fragrant, bitter and nauseating plants utilized in TTM cancer remedy were successfully investigated and identified several lead plants and components with cytotoxic and antiinflammatory activity that require further study. The TTM wind element theory appeared to be aligned with cancer-related activity. Biological activity results of taste from herbs related with The TTM Herbal Flavor theory. The extra-oral locations of flavor receptors are a promising target for biological activity of TTM which require further scrutiny and identified several lead plants and components with cytotoxic and antiinflammatory activities that also require further study.


The mutual extraction industry: drug use and the normative structure of social capital in the Russian far north.
The article contributes to the literature on the role of social networks and social capital in young people's drug use. It considers the structural and cultural dimensions of the 'risk environment' of post-Soviet Russia, the micro risk-environment of a de-industrializing city in the far north of the country and the kind of social capital that circulates in young people's social networks there. Its focus is thus on social capital at the micro-level, the 'bridging' networks of peer friendship groups and the norms that govern them. The research is based on a small ethnographic study of the friendship groups and social networks of young people in the city of Vorkuta in 2006-2007. It draws on data from 32 respondents aged 17-27 in the form of 17 semi-structured audio and video interviews and field diaries. Respondents were selected from friendship groups in which drug use was a regular and symbolically significant practice. The risk environment of the Russian far north is characterised by major de-industrialization, poor health indicators, low life expectancy and limited educational and employment opportunities. It is also marked by a 'work hard, play hard' cultural ethos inherited from the Soviet period when risk-laden manual labour was well-rewarded materially and symbolically. However, young people today often rely on informal economic practices to generate the resource needed to fulfil their expectations. This is evident from the social networks among respondents which were found to be focused around a daily routine of generating and spending income, central to which is the purchase, sale and use of drugs. These practices are governed by norms that often invert those normally ascribed to social networks: reciprocity is replaced by mutual exploitation and trust by cheating. Social networks are central to young people's management of the risk environment associated with post-Soviet economic transformation. However, such networks are culturally as well as structurally determined and may be sites not only of cooperation, support and trust but also of mutual exploitation, deceit and distrust. This does not imply these regions are devoid of social capital. Rather it suggests that the notion of social capital as a natural by-product of a self-regulating economy and its institutions needs to be reconsidered in the context of local configurations of capital and social relations as well as their cultural and normative context. This reconsideration should include further reflection on whether the kinds of social networks described might be better understood not as motors for the generation of social capital but as sites of its 'mutual extraction'.


Leptomeningeal carcinomatosis in a patient with recurrent unresectable squamous cell carcinoma of the retromolar trigone-a brief report.
The reported incidence of leptomeningeal carcinomatosis is 3-8% in patients with solid tumours. More commonly, it has been described in the setting of advanced cancers of the lung, breast and malignant melanoma. A 50-year-old diabetic patient with recurrent unresectable squamous cell carcinoma (SCC) of the right retromolar trigone (rT4bN0M0) presented with severe low backache and weakness in bilateral lower limbs 20 days after the completion of concurrent chemoradiotherapy. Contrast-enhanced MRI of the spine showed multiple nodular enhancing leptomeningeal lesions at the lumbar level and an intramedullary T2/FLAIR-hyperintense longitudinal lesion involving the central cord from C2 to C7 vertebral levels, suggestive of leptomeningeal metastases. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, elevated protein and markedly decreased glucose. The CSF cytology revealed scattered large atypical cells, suspicious for metastasis. Non-contrast MRI of the brain showed a T2/FLAIR-hyperintense lesion involving the right caudate nucleus suggestive of either an acute infarct with haemorrhagic transformation or a haemorrhagic brain metastasis. During assessment, he had high-grade fever and was started on empirical intravenous antibiotics (ceftriaxone, vancomycin and subsequently meropenem) in line with the management for acute bacterial meningitis. Gram staining of CSF did not demonstrate the presence of any bacteria and the specimen was sterile on culture. He did not respond to empirical antibiotics, had a progressive downhill course and eventually died due to aspiration pneumonia. This brief report highlights the importance of awareness of leptomeningeal carcinomatosis as a possible cause of backache with sensorimotor deficit and autonomic dysfunction in a previously treated case of head and neck SCC.


[Cystic testicular anomaly with subsequent stenosis of the small intestine in an emerald tree boa (Corallus caninus L., 1758)].
A case report with emphasis on diagnostic procedures and differential diagnoses is given. The etiology is discussed in comparison to similar malformations in mammals and other reptiles. The literature is reviewed with emphasis on differential diagnostic aspects.


Salvage therapy with tigecycline for recurrent infection caused by ertapenem-resistant extended-spectrum β-lactamase-producing Klebsiella pneumoniae.
Optimal antimicrobial therapy for infections due to ertapenem-resistant Enterobacteriaceae remains undetermined. In this study, a diabetic patient with recurrent pyomyositis and osteomyelitis caused by extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae developed ertapenem resistance after imipenem/cilastatin treatment, which was a currently recommended therapy. He was finally treated successfully using tigecycline. Ertapenem resistance was in part explained by the production of SHV-type ESBL and the absence of an outer membrane protein, OmpK36. Our observation suggests that tigecycline may be an alternative for invasive infections caused by ESBL-producing Enterobacteriaceae with decreased susceptibility to carbapenem.


Heterologous regulation of EGF receptor function in cultured aortic smooth muscle cells.
A10 cultured smooth muscle cells from rat embryonic thoracic aorta bound 125I-labelled epidermal growth factor (125I-EGF), and responded to EGF by an increase in DNA synthesis. Scatchard analysis of binding data obtained at 4 degrees C showed curvilinearity consistent with there being two affinity classes of binding site. The amount of 125I-EGF that bound was decreased by treatment of the A10 cells at 37 degrees C with [Arg8]vasopressin or with 5-hydroxytryptamine (5-HT). Scatchard analysis of binding (at 4 degrees C after pretreatment at 37 degrees C) revealed this effect to be due to a loss of the high-affinity component of 125I-EGF binding, with no change in total receptor number. The presence of vasopressin or 5-HT raised the concentration of EGF required for the stimulation of DNA synthesis. Cultured A10 aortic smooth muscle cells therefore have receptors for EGF that mediate an increase in cell proliferation. EGF receptor function is modified by vasopressin and 5-HT, probably as a consequence of their effects on EGF receptor affinity.


Protective and immunogenic effects of Escherichia coli-expressed infectious pancreatic necrosis virus (IPNV) VP2-VP3 fusion protein in rainbow trout.
Infectious Pancreatic Necrosis Virus (IPNV) is a member of the family Birnaviridae which causes significant losses in the aquaculture industry. To develop a recombinant vaccine for IPNV, a cDNA construct of IPNV VP2-VP3 fusion gene was prepared and cloned into an Escherichia coli (E. coli) expression vector (pET-26b) to obtain recombinant protein products. A study was conducted to determine the antibody responses and protective capacity of this recombinant vaccine expressing VP2-VP3 fusion protein. Subsequently, juvenile rainbow trout were inoculated by injecting purified recombinant IPNV VP2-VP3 proteins, followed by challenge with virulent IPNV in rainbow trout. Our results demonstrate that recombinant E. coli derived VP2-VP3 fusion protein induced a strong and significantly (P < 0.05) higher IgM antibody response in serum samples compared to control groups. Following intraperitoneal challenge, the relative percent survival (RPS) rate of survivors was 83% for the vaccinated group. Statistical analysis of IgM levels indicated that immunogenicity of recombinant VP2-VP3 protein, combined with adjuvant, was much higher than any other groups of rainbow trout challenged with virulent IPNV. This result was confirmed by measuring the viral loads of IPNV in immunized rainbow trout which was drastically reduced, as analyzed by real-time RT-PCR. In summary, we demonstrate that E. coli-expressed IPNV VP2-VP3 injectable vaccine is highly immunogenic and protective against IPNV infection.


Chromosome stability in CHO cells.
The established cell line derived many years ago from Chinese hamster ovary (CHO cells) has been studied for the extent of chromosomal variation. Because this cell line is used extensively for genetic studies, the contribution of chromosome variability to genetic variability has also been examined. The quasidiploid CHO cells were found to have a banded karyotype somewhat altered from that of the Chinese hamster from which the line was derived. However, most of the genome could be accounted for among the rearranged marker chromosomes. In addition, the CHO line was found to have a relatively stable karyotype, the same basic karyotype being found in a majority of the uncloned cells, as well as in most cells of several but not all independent clones. Many, but not all, mutant cell lines derived from CHO also showed the same basic karyotype. Quasitetraploid cells, derived either spontaneously or by Sendai-virus-induced fusion, showed considerably more variation resulting in loss or gain of whole chromosomes, rearrangement of chromosomes, and appearance of new "marker" chromosomes.


A sensitive one-step real-time RT-PCR method for detection of deformed wing virus and black queen cell virus in honeybee Apis mellifera.
A one-step real-time RT-PCR based on SYBR Green (SG) chemistry was developed for the detection, differentiation and quantification of two of the most common viruses on the honeybee Apis mellifera L., deformed wing virus and black queen cell virus. Two sets of primers specific for each virus, were designed in conserved regions of the viral genome for their use in the one-step real-time RT-PCR. Both reactions were optimized for highest sensitivity and specificity and SG-based real-time was used to achieve quantitative detection. All samples evaluated in this study were from Spanish honeybee colonies. Viral detection and identification was confirmed by sequencing of the PCR products. The described one-step real-time SG RT-PCR proved to be a fast, accurate and useful technique to detect and even quantify these honeybee viruses that cause unapparent infections, and might contribute with other factors to the increasing honeybee colonies depopulation.


Ultrasonication and microwave pre-treated locust protein hydrolysates enhanced the storage stability of meat emulsion.
Locust protein hydrolysates (LoProHs) pre-processed with microwave and ultrasonication were developed and evaluated for their potential for enhancing the quality of the stored meat emulsion (MEmul). Locust protein (LoPro) samples pre-processed with ultrasonication (Ult) or microwave (Mic) or with no treatment (Not) were hydrolysed with alcalase enzyme (3%). The microwave pre-processed (Mic-LoProHs) and ultrasonicated (Ult-LoProHs) hydrolysates showed significantly (P < 0.05) higher antioxidant [FRAP (ferric reducing antioxidant power) and ABTS and DPPH radical scavenging activities] and antimicrobial [minimum inhibitory concentration (MIC) and inhibitory halos (mm)] potential. The MEmul samples incorporated with Mic-LoProHs and Ult-LoProHs at the maximum level of 1.5% exhibited significantly (P < 0.05) improved results for all the quality parameters such as antioxidant potential (FRAP, ABTS and DPPH), protein oxidation (total carbonyl content), lipid stability, and microbial quality during refrigerated storage (4 ± 1 °C) of two-weeks compared to the control MEmul without any LoProHs. A positive (P < 0.05) impact of the LoProHs was found on the sensory quality of MEmul samples after one week of storage. The digestion simulation improved (P < 0.05) the antioxidant potential of the MEmul samples.


Toxicity of single and combined 4-epianhydrotetracycline and cadmium at environmentally relevant concentrations on the zebrafish embryos (Danio rerio).
The combined pollution of antibiotics and heavy metals has attracted a worldwide attention in the recent years. 4-epianhydrotetracycline (EATC) is the major degradation product of tetracycline (TC), which has been detected frequently in environment and its concentration is even higher than TC under some circumstances. Cadmium (Cd) is a common heavy metal contaminant and has highly toxic to organisms, plants and humans even at low doses. In the present study, zebrafish (Danio rerio) embryo toxicity test was performed to investigate the single and combined effects of EATC and Cd on aquatic organisms. Exposure to EATC and Cd at environmentally relevant concentrations had a series of hazardous impacts on the embryonic development, including lethality, hatching rate, heart rate and teratogenic effects. Compared to the contaminant existed alone, combined pollution produced stronger toxicity, which appeared as the decreasing of heart rate and hatching rate, and the increasing of malformation of zebrafish embryos. After 96 h exposure, the reactive oxygen species (ROS) levels in zebrafish embryos were increased significantly, revealing that EATC-Cd co-exposure resulted in potential oxidative stress-induced damage. Acridine orange (AO) staining showed that combined exposure resulted in stronger cell apoptosis. The potential health risks of the combined pollution of EATC and Cd should be paid more attention to higher level vertebrates and humans.


Effect of hybridization composition and glycerin content on novel corn starch/nata de coco plastic film: Thermal, mechanical, and degradation study.
The objective of this work was to develop a plastic film from food sources with excellent thermal, mechanical, and degradability performance. Corn starch (CS)/nata de coco (NDC) were hybridized with addition of glycerin as plasticizer at different weight ratio and weight percent, respectively. Sample analysis found that the hybridization of CS with NDC improved the film forming properties, mechanical and thermal, degradation properties, as well as hydrophobicity and solubility of the film up to 0.5:0.5 wt hybrid ratio. The properties of the films were highly affected by the homogeneity of the sample during hybridization, with high NDC amount (0.3:0.7 wt CS:NDC) showing poor hydrophobicity, and mechanical and thermal properties. The glycerin content, however, did not significantly affect the hydrophobicity, water solubility, and degradability properties of CS/NDC film. Hybridization of 0.5:0.5 wt CS/NDC with 2 phr glycerin provided the optimum Young's modulus (15.67 MPa) and tensile strength (1.67 MPa) properties.


Retracted: Construction of Financial Management Early Warning Model Based on Improved Ant Colony Neural Network.
[This retracts the article DOI: 10.1155/2021/6748920.].


Color Doppler Ultrasound Assessment of Subclinical Activity With Scoring of Morphea.
Detection of activity in morphea is paramount for adequately managing the disease. Subclinical ultrasound involvement on inactive lesions or healthy skin areas adjacent to morphea has not been described to date. The study aimed to detect morphea's subclinical activity by Color Doppler ultrasound not identified with the clinical scorings. This cross-sectional retrospective study was done from January 2014 to July 2019 in patients with a clinicopathological diagnosis of morphea. The modified Localized Scleroderma Skin Severity Index (mLoSSI) and The Ultrasound Morphea Activity Score (US-MAS) were used to correlate clinical and subclinical activity. A total of 36 patients met the inclusion criteria. 54% of cases presented subclinical activity in areas adjacent to the clinically active lesion, 23% in nonadjacent regions, and 23% demonstrated activity at a clinically inactive lesion site.100% of patients with morphea "en coup de sabre" involving the frontal region of the face concomitantly presented both subclinical activities of morphea on the frontal facial region and the scalp following the same axis.A positive relationship was observed between the degree of clinical activity measured by mLoSSI and US-MAS scoring.The main limitations of our study were the low number of patients and the inability to detect alterations < 0.1 mm. Subclinical activity is frequent in morphea, can extend beyond the lesional areas, including apparently noninvolved adjacent and distant corporal regions, and can be detected by color Doppler ultrasound.


Healthcare providers' perspectives of disrespect and abuse in maternity care facilities in Nigeria: a qualitative study.
To explore healthcare providers' perspectives of disrespect and abuse in maternity care and the impact on women's health and well-being. Qualitative interpretive approach using in-depth semi-structured interviews with sixteen healthcare providers in two public health facilities in Nigeria. Interviews were audio-recorded, transcribed, and analysed thematically. Healthcare providers' accounts revealed awareness of what respectful maternity care encompassed in accordance with the existing guidelines. They considered disrespectful and abusive practices perpetrated or witnessed as violation of human rights, while highlighting women's expectations of care as the basis for subjectivity of experiences. They perceived some practices as well-intended to ensure safety of mother and baby. Views reflected underlying gender-related notions and societal perceptions of women being considered weaker than men. There was recognition about adverse effects of disrespect and abuse including its impact on women, babies, and providers' job satisfaction. Healthcare providers need training on how to incorporate elements of respectful maternity care into practice including skills for rapport building and counselling. Women and family members should be educated about right to respectful care empowering them to report disrespectful practices.


Zinc deficiency amongst adolescents in Delhi.
A cross sectional study was conducted in 260 adolescent schoolchildren (114 males) in the age group of 11-18 years to estimate the prevalence of zinc deficiency in the National Capital Territory of Delhi. Serum zinc was estimated using Inductively coupled plasma mass spectrometer. Overall, 49.4% children (50.8% males, 48.2% females) were found to have a deficient zinc nutriture.


Mechanism of emergence of hepatitis B virus escape variants: approaches to prevention.
Hepatitis B virus causes a chronic infection in a large proportion of cases. One possible mechanism whereby hepatitis B avoids the host defences is by mutation of antigenic epitopes. This article reviews current views in the area.


Opiate substitution treatment to reduce in-prison drug injection: a natural experiment.
There is emerging evidence that opiate substitution treatment (OST) in prison is associated with reduced injecting drug use (IDU). In Australia OST is available in prison for men and women in all jurisdictions except Queensland, where it is available only for women. The aim of this study was to examine the association between in-prison OST and in-prison IDU in New South Wales (NSW) and Queensland. Cross-sectional survey of Australian prisoners in NSW (N=1128) and Queensland (N=1325). Lifetime IDU and in-prison IDU measured by self-report. Lifetime history of IDU was significantly more common among females than males in both jurisdictions. Among those with a lifetime history of IDU, the lifetime prevalence of in-prison IDU was significantly higher for males than females in both jurisdictions, however the magnitude of this sex difference was considerably greater in Queensland than in NSW. Provision of OST in prison is associated with a reduced lifetime prevalence of in-prison drug injection, among those with a lifetime history of IDU. Irrespective of OST policies, women with a history of IDU are less likely than their male counterparts to inject in prison; reasons for this novel and replicable sex difference require further examination.


The effect of resveratrol on signal transduction pathways and the role of pro-apoptotic Bax protein on apoptosis in HCT- 116 colon carcinoma cell lines.
Colon carcinoma is the third among the cancer related deaths. The role of pro-apoptotic Bax protein on the resveratrol related apoptosis, mitochondrial membrane potential and signal pathways has not been identified in colon carcinoma cells. In this direction, HCT-116 bax positive and HCT-116 negative cell lines were utilized to detect the apoptotic effect and I?B, MEK1 and STAT 3 signal transduction pathways of resveratrol. The impact on the cell viability and IC50 value of resveratrol has been determined via WST-1 viability assay. The ratio of apoptosis has been evaluated via flow cytometry following Annexin V/Propidium iodide (PI) double staining. Changes in the mitochondrial membrane potential have been analyzed by flow cytometry and JC-1 fluorometric staining. IkB, MEK1 and STAT3 molecules were measured by Enspire device. Data showed the IC50 value for resveratrol as 50M. According to the flow cytometry, apoptosis ratio has been determined as 29.65% in the experimental group of bax positive cells, as 13.98% in the experimental group of bax negative cells. Changes in the membrane potential has been established as 8.62% in the experimental group of bax positive cells, as 97.98% in the experimental group of bax negative cells. When the obtained data from Enspire device was reviewed; bax positive cells I?B phosphorylations were found as as 5.22 for experimental groups; MEK1 phosphorylations were found as and as 1.15 for experimental groups; STAT 3 phosphorylations were found as and as 2.52 for experimental groups. In HCT-116 bax negative cells, I?B phosphorylation were and 2.71 in experimental groups; MEK1 phosphorylation were 1.18 in experimental groups; STAT 3 phosphorylation were 1.54 in experimental groups. Our data show that Bax protein plays role in the apoptotic effect of resveratrol by altering mitochondrial membrane potential and mitochondrial membrane permeability, signal transduction and the absence of Bax increase the sensitivity of HCT-116 colon carcinoma cells to apoptosis.


Spontaneous resumption of sinus rhythm in an elderly patient after 13 years of permanent atrial fibrillation.
One female patient--with slight pure mitral stenosis, mild hypertension and ischemic cardiomyopathy and disabling pulmonary emphysema--developed at 54 years of age permanent atrial fibrillation, had a gratuitous mitral commissurotomy four months later, sustained chronic fibrillation for 13 years, then spontaneously resumed sinus node command at age 67 without any discernible reason. Sinus rhythm was being maintained at follow-up nine months later. Her cardiac status of fair compensation under modest digitoxin and diuretic therapy has neither improved nor worsened with the return of atrial systole. The duration, in this observation, of permanent auricular fibrillation before spontaneous return of sinus rhythm, is one of the longest ever published, exceeded, to the best of my knowledge, only by one case of Lewis and by another one of Reeve and associates. Such an exceptional event points out a fascinating enigma: how can major longstanding atrial dysrhythmias (fibrillation, flutter), whose causes and pathogenesis seem at least partly elucidated, spontaneously disappeer in atria so badly diseased? I think we must humbly confess that no satisfactory explanation is at present available for this disconcerting phenomenon.


Prognostic implications of inactive status in highest urgency categories among heart transplantation recipients in the new donor heart allocation system.
Patients on the waiting list for heart transplantation (HT) can become inactive or made status seven because of medical reasons, such adverse events, complications, or psychosocial circumstances. If the condition that caused the inactivation is resolved, patients are re- activated. Information about the prognostic implications of Status 7 in the new donor heart allocation system has not been described. To bridge this knowledge gap, we performed an analysis of the United Network of Organ Sharing (UNOS) registry. Data on adult patients who underwent HT between October 18th, 2018 and October 2021, were queried from the UNOS registry. The main outcomes were post- transplant all-cause mortality, 1-year all-cause mortality and treated acute rejection. Since re-transplantation is a competing event for all-cause mortality, we performed competing risk survival analysis and reported sub distribution hazard ratios (SHR) from the Fine and Gray model to examine the relationship between inactive status and all-cause mortality. A total of 5267 adult patients underwent HT and were previously listed as Status 1 or Status 2 in the new allocation system. We identified 946 HT recipients temporarily inactivated while on HT list (18%). The number of temporarily inactive patients remained stable since the implementation of the new donor allocation system (p = .37). Approximately, two-thirds of temporarily inactive patients (65.9%) were inactivated for being too sick, whereas other frequent justifications for inactivity included left ventricular assist device implantation (7.8%) and insurance related issues (4.8%). Temporarily inactive HT recipients were more likely to be African Americans, males, have a higher body mass index (BMI) and significantly longer waiting time (391.6 ± 600 vs. 72.3 ± 223 days, p < .001) compared with never inactivated patients. In the unadjusted analyses 30-day mortality did not differ between groups, but both 1-year and overall all-cause mortality was significantly higher in temporarily inactive patients (1-year: SHR: 1.3; 95% confidence intervals [CI]: 1.03, 1.64; p = .028, overall mortality SHR: 1.31; 95% CI: 1.06, 1.64; p = .014). After adjustment for donor and recipient characteristics, a trend towards higher 1-year and overall mortality remained (1-year: SHR 1.32; 95% CI .99, 1.76, p = .006, overall mortality SHR: 1.29; 95% CI: .98-1.68, p = .065). No differences in treated acute allograft rejection at 1 year were found between groups. Temporary inactive status while waiting for HT occurs in approximately one in five HT recipients listed in higher urgency categories after the implementation of the new allocation system. A signal of adverse long-term outcomes was found, and this could be explained by differences in recipient characteristics. Further research is required to elucidate pathways involved and possible implications for clinical practice.


Esophageal manometric studies in patients with myasthenia gravis.
Dysphagia is often present early, with varying degrees of involvement, in patients with myasthenia gravis. Twenty-five patients with a clinical status of myasthenia gravis were graded according to a modified Osserman classification and the esophageal manometric results were reported according to their clinical status. The results were also compared with those in 20 normal control subjects. Twenty-four patients (96%) had abnormal motility. The only patient who was in class I had a normal tracing. There was no significant difference in function of the lower esophageal sphincter, but a significant decrease in mean amplitude (15.1 +/- 6.1 versus 29.7 +/- 4.7 mm Hg) and a prolongation in mean duration of the peristaltic wave (7.4 +/- 2.8 versus 4.5 +/- 0.2 seconds) was noted in the upper esophagus. The cricopharyngeal sphincter pressure also showed a significant decrease (23.4 +/- 9.5 versus 43.1 +/- 3.1 mm Hg), but relaxation and coordination were good. The mean amplitudes, mean duration of peristaltic waves, and cricopharyngeal pressures between the myasthenic and control populations were statistically significant, with a p value of 0.001. Besides this, frequent spontaneous contractions, simultaneous contractions, and biphasic repetitive contractions typical of peristaltic dysfunction were also found in myasthenic patients. Motor dysfunction of the esophagus as assessed by manometric study correlates well with Osserman's modified clinical classification.


Growth pattern of axons in the optic nerve of chick during myelogenesis.
The purpose of this experiment was to study the diameter of axons at the time of the initiation of myelin and the pattern of growth of axons in the optic nerve of the chick. Embryos between 15 and 20 days and chicks 3, 5, 22 and 60 days of age were studied on the electron microscopic level. Based on axon diameter a unimodal distribution of unmyelinated axons is present through day 20 of incubation with a mean of approximately 0.35 micrometer. This population is represented through 22 days of age but from day 3 on, a second distinct population of unmyelinated axons is present which has a mean diameter that is approximately twice that of the smaller unmyelinated axons. All axons do not increase simultaneously in diameter but once growth starts, the unmyelinated axons apparently double in diameter at a relatively rapid rate prior to myelination. On incubation day 17 less than 1% of the axons in the optic nerve is myelimated. The number of axons in this group and their diameter (mean approximately 1.2 micrometer) remain relatively constant through day 3 but from days 5 through 22, two distinct populations of myelinated axons are present. By day 60, three distinct distributions of myelinated axons are present with mean diameters of 0.51 micrometer, 1.76 micrometer, and 3.90 micrometer. These populations represent approximately 20%, 67%, and 13% respectively of the total fiber population. As age increases the diameter of some myelinated axons is as small as or smaller than the unmyelinated axons at an earlier period in development. This suggests that factors other than axon diameter might be involved in the start of myelination. It appears that the increase in axon diameter does not occur in a continuous manner but in a saltatory manner from one size to another.


Subacute combined degeneration of the spinal cord masking motor neuron disease: a case report.
Subacute combined degeneration of the spinal cord is a potentially reversible myelopathy typically associated with vitamin B12 deficiency. There is predominant involvement of spinal cord posterior and lateral tracts, and manifestations include peripheral paraesthesia, impaired proprioception, gait disturbance, neuropathy and cognitive changes. Motor neuron disease (MND) is an unremittingly progressive neurodegenerative disorder involving upper and lower motor neurons with an average prognosis of 2-3 years. The diagnosis is clinical and may be supported by electromyography. A subset of MND occurs concurrently with frontotemporal dementia (FTD-MND) and may be initially misdiagnosed as a primary psychotic disorder. We describe a 57-year-old Caucasian woman who presented with confusion and dysarthria. Low vitamin B12 levels and MRI findings led to an initial diagnosis of subacute combined degeneration of the spinal cord. Despite treatment, persistent dysarthria and presence of both upper and lower motor neuron signs on clinical examination prompted further assessment. Electromyography supported the diagnosis of MND. Comorbid chronic paranoid schizophrenia complicated the diagnostic process. We discuss overlapping features between B12 deficiency and MND as well as the neuropsychiatric overlap of B12 deficiency, FTD-MND and chronic schizophrenia. Firstly, variability in neurocognitive and imaging manifestations of B12 deficiency can limit delineation of other pathologies. Failure to improve following correction of nutritional deficiencies warrants further investigation for an alternate diagnosis. Secondly, re-evaluation of patients with comorbid mental health conditions is important in reaching timely and accurate diagnoses.


Evidence for a projection from the lateral preoptic area and substantia innominata to the 'mesencephalic locomotor region' in the rat.
A series of anatomical and electrophysiological experiments have been carried out to examine the organization of a direct projection from the substantia innominata and the lateral preoptic area of the hypothalamus, referred to collectively as the subpallidal region, to the pedunculopontine nucleus and adjacent parts of the dorsal midbrain in the adult rat. In the first series of experiments, the retrogradely transported fluorescent tracer SITS, which does not appear to be taken up by fibers-of-passage, was injected into the pedunculopontine nucleus, and the distribution of labeled neurons was plotted in the substantia innominata and lateral preoptic area, as well as in adjacent regions including the medial preoptic area, the bed nucleus of the stria terminalis and parvocellular parts of the paraventricular nucleus. Then, the anterogradely transported lectin PHA-L, which also does not appear to be taken up in effective amounts by fibers-of-passage, was injected into parts of the substantia innominata and lateral preoptic area that project directly to the pedunculopontine nucleus. These experiments demonstrated that fibers from both regions descend through the medial forebrain bundle and give rise in the pedunculopontine nucleus to a terminal field that contains many structures with the appearance of terminal boutons. They also indicated that individual fibers from the subpallidal region innervate both the pedunculopontine nucleus and adjacent parts of the central gray, and that the pathway innervates areas along the length of the medial forebrain bundle on its way to the dorsal midbrain. In a third series of experiments the retrogradely transported fluorescent tracer True Blue was injected into upper thoracic levels of the spinal cord, and it was found that the region of the pedunculopontine nucleus that receives the densest input from the subpallidal region contained many retrogradely labeled neurons on both sides of the brain. And finally, a series of electrophysiological experiments demonstrated that single-pulse stimulation of the substantia innominata and the lateral preoptic area altered the firing rate of a majority of the neurons in and around the pedunculopontine nucleus, and that excitatory and inhibitory responses occurred about equally. These results clearly suggest that the subpallidal region projects directly to the pedunculopontine nucleus and adjacent regions including the central gray and the superior colliculus.(ABSTRACT TRUNCATED AT 400 WORDS)


Prenatal diagnosis of cleft lip and/or palate: What do we tell prospective parents?
Cleft lip and/or palate (CL/CP) is the most common congenital craniofacial anomaly and parents often ask, "how did this happen?" Patients and families may benefit from access to a multidisciplinary team (MDT) from prenatal diagnosis into early adulthood. Multiple factors can contribute to the development of a cleft. We discuss the epidemiology and risk factors that increase the likelihood of having a newborn with a cleft. The purpose of this article is to review the prenatal investigations involved in the diagnosis and workup of these patients in addition to postpartum treatment, prognostic factors, and counseling families regarding future recurrence risk.


NODDI in clinical research.
Diffusion MRI (dMRI) has proven to be a useful imaging approach for both clinical diagnosis and research investigating the microstructures of nervous tissues, and it has helped us to better understand the neurophysiological mechanisms of many diseases. Though diffusion tensor imaging (DTI) has long been the default tool to analyze dMRI data in clinical research, acquisition with stronger diffusion weightings beyond the DTI regimen is now possible with modern clinical scanners, potentially enabling even more detailed characterization of tissue microstructures. To take advantage of such data, neurite orientation dispersion and density imaging (NODDI) has been proposed as a way to relate the dMRI signal to tissue features via biophysically inspired modeling. The number of reports demonstrating the potential clinical utility of NODDI is rapidly increasing. At the same time, the pitfalls and limitations of NODDI, and general challenges in microstructure modeling, are becoming increasingly recognized by clinicians. dMRI microstructure modeling is a rapidly evolving field with great promise, where people from different scientific backgrounds, such as physics, medicine, biology, neuroscience, and statistics, are collaborating to build novel tools that contribute to improving human healthcare. Here, we review the applications of NODDI in clinical research and discuss future perspectives for investigations toward the implementation of dMRI microstructure imaging in clinical practice.


Pancreatic tuberculosis: case report and review of the literature.
Tuberculosis affecting the pancreas is rare. Its occurrence may pose diagnostic problem in differentiating from carcinoma of the pancreas. It usually is a welcome pathological surprise. A case of tuberculosis affecting the pancreas is reported which presented as a case of obstructive jaundice. The response of the disease to antituberculous drugs is good.


Biomimic Binding Affinity Gradients Triggered GSH-Response of Core-Shell Nanoparticles for Cascade Chemo/Chemodynamic Therapy.
In eukaryotes and prokaryotes, some copper transportations driven by gradient copper-binding affinities exhibit typical glutathione (GSH)-responsive features. Inspired by these delicate endogenous processes, a biomimic copper-ion mediated GSH-responsive nanomedicine is designed based on the gradient copper-binding strengths between polydopamine (PDA) species and GSH. The nanomedicine is constructed as core-shell nanoparticles with copper-polydopamine (Cu-PDA) coordinated shell and micellar core encapsulating chemotherapeutic drug of β-lapachone (β-lapa). In tumor cells, the excess intracellular GSH will reduce and extract the Cu(II) from the Cu-PDA network, triggered by the binding affinity gradients between Cu-PDA and Cu-GSH, resulting in the breaking of the shell and the releasing of β-lapa and Fenton agent copper. The additional Fenton reaction of copper ions induces excess oxidative damage of tumor cells assisted by the abundant H2 O2 amplified by β-lapa, achieving cascade anticancer effects combining chemodynamic therapy with chemotherapy. This multilevel anticancer system exhibits an efficient tumor inhibitory rate and a negligible systematic toxicity for normal organs in vivo, presenting a new bioinspired GSH-responsive strategie to develop stimuli-responsive structures.


CT-guided radiofrequency ablation of painful intra-articular osteoid osteoma in children: Is there a concern for cartilage damage?
To evaluate the safety and efficacy of computed tomography-guided percutaneous radiofrequency ablation (PRFA) in the management of uncommon and technically challenging intra-articular osteoid osteoma in children. From December 2018 to September 2022, 16 children with intra-articular osteoid osteoma, including ten boys and six girls, were treated at two tertiary centers with percutaneous CT-guided RF ablation using a straight monopolar electrode. The procedures were carried out under general anesthesia. Post-procedural clinical outcomes and adverse events were assessed through clinical follow-up. Technical success was achieved in all of the participating patients. Clinical success with relief of symptomatology throughout the period of follow-up was achieved in 100% of the patients. No persistence or recurrence of pain occurred during the follow-up period. No immediate or delayed adverse effects were observed. PRFA is shown to be technically feasible. Clinical improvement can be achieved with a high rate of success in the treatment of children with difficult-to-treat intra-articular osteoid osteomas.


Trends in middle-aged women's reports of symptoms, use of hormone therapy and attitudes towards it.
To investigate changes in middle-aged women's attitudes towards hormone therapy (HT), use of HT and reports of symptoms between 1995 and 2003. All women (n = 2209) in two primary health-care districts received a questionnaire, when aged 45, 50, 55 or 60. The questionnaire consisted of quality of life instruments and items concerning menopause, health, symptoms, attitudes towards HT and use of it. A total of 1681 women (76%) responded to the questionnaire. Thirty-one percent had used HT, with a mean duration of 4 years. A shift from mainly positive attitudes towards HT and increasing use of HT in the 1990s to largely negative attitudes and decreasing use became evident in 2002-2003. In comparison, current HT users in 2002-2003 were older and had used HT for longer than users in previous years. The number of general symptoms reported tended to increase successively and satisfaction with health to decrease during the period. Women with a history of HT continuously reported a greater number of symptoms than those women who had never used it. Reports of vasomotor symptoms did not change over time. The changes that have occurred in beliefs regarding HT have had an impact both on attitudes towards HT and on use of HT among the women we surveyed. The increase in number of general symptoms is discussed in relation to perception of menopause, prescription patterns of HT and changes at the societal level.


Treatment of nanowaste via fast crystal growth: with recycling of nano-SnO2 from electroplating sludge as a study case.
The treatment of industrial sludge containing amorphous/nanophase metal oxides or hydroxides is one of the vital issues in hazardous waste disposal. In this work, we developed a strategy to recycle nano-SnO(2) from tinplate electroplating sludge. It revealed that the major components of this sludge were acid soluble Sn and Fe amorphous phases. By introducing NaOH as a mineralizer, a fast growth of amorphous Sn compound into acid-insoluble SnO(2) nanowires was achieved selectively. Thus, the as-formed nano-SnO(2) could be recycled via dissolving other solid compositions in the sludge by using acid. The role of NaOH on accelerating both the Oriented Attachment (OA) and Ostwald Ripening (OR) growth of SnO(2) was discussed, which was regarded as a critical factor for treating the sludge. A pilot-scale experiment was conducted to treat 2.3 kg original sludge and the recycling of about 90 g nano-SnO(2) was achieved. We anticipate this work can provide a good example for the recycling of valuable metals from industrial sludge containing fine metal oxides or hydroxides.


An experimental comparison of three courses in history-taking skills for medical students.
Since clinical training often fails to equip medical students with essential history-taking skills, more effective teaching methods required to be developed. As previous work had suggested that training which included televised demonstrations of history-taking and practice with simulated patients might be superior to traditional methods, it was decided to evaluate this experimentally. Thirty students beginning the Oxford Clinical Course were randomly selected and allocated to a traditional or one of two experimental courses. Both experimental courses used television and simulation but differed in the way the history-taking demonstrations were presented. After completing these courses, each student was asked to take a history from a simulated patient. Rating of the videotapes of these interviews showed that the two experimental groups obtained much more information and used many more of the required skills than students assigned to the traditional course. The experimental students were also rated more favourably by the simulators and recorded more data in their case histories. It is concluded that these short courses were practical, very effective, and could be augmented by a self-teaching programme in history-taking skills.


Treatment of myoclonic dystonia with transcutaneous electrical nerve stimulation.
The use of a transcutaneous nerve stimulator yielded positive results in a condition marked by involuntary movements (tremors and myoclonias) and dystonia. In the absence of clues to the pathophysiology of the myoclonus and dystonia, it is argued that transcutaneous stimulation induces an action on the neurotransmitters that inhibits neuromuscular function.