Relationship of "prodromal" symptoms with severity and type of psychopathology in the active phase of schizophrenia.
Both retrospective and prospective studies have identified a broad spectrum of "prodromal" symptoms, but their relationship to those of frank psychosis remains largely unexplored. In 73 successive hospitalized patients with schizophrenia in the first or second psychotic episode and with duration of illness 3 years or less from the onset of psychosis, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I diagnoses were made. In addition, within the first 5 days from the psychotic episode's onset, symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS). Stepwise regression analyses showed that 8 prodromal symptoms carried an increased risk for high total PANSS and the components of the PANSS scores, independently of sex; 1 symptom was associated with mild psychopathology. However, the categories of negative- and positive-disorganization prodromal symptoms were not associated with the corresponding PANSS components. Similar findings were observed in the nonparanoid patients, whereas in the paranoid, only 2 nonspecific symptoms were associated with high PANSS psychopathology. In addition, there were significant associations between number of prodromal symptoms and total PANSS and the subscales positive and general scores in the patients with the nonparanoid subtypes, but there were not such associations in those with the paranoid. Several prodromal symptoms, as well as the number of symptoms, are associated with the severity of the psychopathology of frank psychosis. In the nonparanoid subtypes there is a continuance in the transition from the prepsychotic to the psychotic stage, whereas in the paranoid, the transition appears to be disrupted.


Crystallization and preliminary diffraction analysis of a group I ribozyme from bacteriophage Twort.
Group I introns are catalytic RNAs that are capable of performing a variety of phosphotransesterification reactions including self-splicing and RNA cleavage. The reactions are efficient, accurate and dependent only on the presence of guanosine-nucleotide substrate and sufficient magnesium ion to stabilize the structure of the RNA. To understand how the group I intron active-site facilitates catalysis, crystals of a 242-nucleotide ribozyme bound to a four-nucleotide product RNA have been produced that diffract to 3.6 A resolution. The space group of these crystals is I2(1)2(1)2(1) and the unit-cell parameters are a = 94.6, b = 141.0, c = 210.9 A. A single heavy-atom derivative has been synthesized by covalent modification of the product RNA with iodine.


[Conservative therapy of arterial occlusive diseases. Double-blind study on the effect of butalamine hydrochloride].
In a double blind placebo-controlled trial the influence of butalamine-hydrochloride (Adrevil forte) in a daily dosage of 3 x 2 tablets on the exercise tolerance of muscles with impaired blood flow in the lower limb was evaluated. The drug was tested versus placebo in a total of 32 patients suffering from peripheral arterial insufficiency stadium II according to Fontaine with occlusions in one or both extremities. Clinical parameters measured were muscle ergometry, plethysmography as well as the assessment of the painfree walking distance. During the whole trial the systemic blood pressure was monitored. The group receiving the active drug showed already after two weeks therapy a statistically significant improvement in the walking distance. After the end of 8 weeks therapy the walking distance in the group under active drug therapy was increased 4 times. Measurements of perfusion also showed significantly higher values under active therapy. The systemic blood pressure was not affected during the 8 weeks therapy with Adrevil forte.


[Saw injury of the hand--an accident with grave sequelae].
Besides bruises saw injuries of the hand are the most common severe hand injuries. A total of 294 of 400 patients who had a saw injury between 1982 and 1986 were monitored in the course of a followup examination spanning the time of the accident up to re-entry into professional life. Causes of accidents as well as injury patterns, surgical treatment and aftereffects were analysed. The high number of injuries (70.8%) sustained while not working was remarkable as well as the fact that despite the seriousness of the injury 64.6% of the patients were content with the cosmetic results of treatment and 65% satisfied with the recovered function of the injured hand.


Ultrasensitive quantification of serum vitamin D metabolites using selective solid-phase extraction coupled to microflow liquid chromatography and isotope-dilution mass spectrometry.
The capacity for quantification of active metabolites of vitamin D (VitD) is highly valuable to evaluate the risks and therapies for numerous diseases such as multiple sclerosis. However, the extremely low circulating levels and poor detectability of some dihydroxyl metabolites such as the 1alpha,25-dihydroxy-VitD(3) constitute a daunting challenge. Based on the combination of a selective solid-phase extraction (SPE) and a microflow liquid chromatography tandem mass spectrometry (microLC-MS/MS), we developed an ultrasensitive method for the robust, selective, and accurate quantification of four key VitD metabolites, including 25-hydroxy-VitD(2), 25-hydroxy-VitD(3), 24(R),25-dihydroxy-VitD(3), and 1alpha,25-dihydroxy-VitD(3), in serum samples. A one-step derivatization was employed to improve the ionization efficiency of the metabolites. The SPE procedure was optimized so that the analytes were selectively extracted from serum, while the sample matrix was substantially simplified. By eliminating majority of undesirable compounds from the matrix, the selective SPE enabled a high sample loading volume on the microLC column without causing overcapacity of the microLC column and thus helped to achieve ultralow detect limits in serum. An on-column sample focusing approach was employed to prevent band-broadening, and a sufficient microLC separation was achieved to eliminate endogenous interferences and to minimize ion suppression effect. Detect limits of the four metabolites ranged from 0.5-1 pg/mL, and the linearity was excellent for all compounds. The method showed high quantitative accuracy (error < 13.8%) and precision (CV < 14.1%). For 1alpha,25-dihydroxy-VitD(3), a lower limit of quantification (LLOQ) of 5 pg/mL was validated. This high level of sensitivity, for the first time, enabled the robust and consistent LC/MS/MS-based analysis of the four metabolites in a large-scale clinical investigation. Serum samples from 281 multiple sclerosis patients and 22 healthy subjects were analyzed, and it was discovered that the levels of both 24(R),25-dihydroxy-VitD(3) and 1alpha,25-dihydroxy-VitD(3) were significantly lower in patients than healthy subjects (P < 0.05). This novel observation may imply that the incidence of multiple sclerosis is inversely associated with the levels of the two metabolites. Moreover, the method was highly robust and reproducible as evaluated extensively in the clinical analysis; therefore, it could serve as a more selective and accurate alternative to immunoassay for large-scale clinical studies.


Anal Sphincter Defect and Fecal Incontinence.
Anal sphincter defects can lead to fecal incontinence. The relationship between the extent of defect and continence is controversial. Magnetic resonance imaging (MRI) of the pelvis can assess anal sphincter defects. Transrectal ultrasonography (TRUS) is used to assess sphincter integrity in adults. We present a 17-year-old male with history of sexual abuse, rectal prolapse, and fecal incontinence. MRI showed a small defect that did not explain his clinical presentation. TRUS identified more extensive defects which were not picked up by MRI. The patient had rectopexy, and his rectal prolapse and fecal incontinence resolved. TRUS was superior in identifying sphincter defects compared with MRI. Our case also highlights that continence is possible despite large sphincter defects in pediatric patients. This may reflect the compensatory mechanism of residual sphincter in the absence of the aggravating factors like rectal prolapse.


The anti-HIV pentameric pseudopeptide HB-19 is preferentially taken up in vivo by lymphoid organs where it forms a complex with nucleolin.
The HB-19 pseudopeptide 5[Kpsi(CH(2)N)PR]-TASP, psi(CH(2)N) for reduced peptide bond, is a specific inhibitor of HIV infection in different CD4(+) cell lines and in primary T-lymphocytes and macrophages. It blocks virus-particle attachment to permissive cells by binding and forming a stable complex with nucleolin expressed on the cell surface. Here, we have investigated the tissue distribution of the tritiated HB-19 by using beta-radio imager whole-body mapping in rats. A rapid, selective, and stable distribution and accumulation of the systematically administered HB-19 was demonstrated within the spleen, liver, bone, and kidney as soon as 5 min following its administration. No apparent uptake of HB-19 occurred in the brain and the muscle tissue. Interestingly and despite its rapid clearance from the blood, at 24 h postexposure a significant proportion of HB-19 was still recovered from target organs, of which 16-37% could be accounted for intact pseudopeptide. The elimination of HB-19 mainly occurred by renal glomerular filtration and most of the excreted radioactivity appeared to be HB-19 metabolites. Finally, injection of the biotin-labeled HB-19 pseudopeptide but not its control counterpart allowed the recovery of the HB-19-nucleolin complex from the liver, spleen, thymus, and bone marrow, thus indicating that the in vivo molecular target of HB-19 is surface nucleolin. Our results demonstrate the preferential uptake and stability of HB-19 in lymphoid organs that are the site of HIV propagation.


Amyand's hernia in infant: a rare entity.
The chance of vermiform appendix lying with in a hernial sac is 1% or less and is known as Amyand's hernia and it is very rare in infant and neonate. Till date, only twenty cases had been reported in English literature. We are reporting a rare case of Amyand's hernia where appendix was present in right inguinal sac of non-obstructed inguinal hernia in a seven month old male infant during operation. The appendectomy was done along with right inguinal herniotomy. In most of the reported cases, appendix was inflamed or perforated, expect in one case where appendix was not inflamed but patient presented with inguinal hernia. This case is reported because of the rarity of Amyand's hernia in infant, the appendix was not inflamed, hernia was not obstructed, and whether in such types of cases appendix should be preserved or not.


[Cerebral metastasis of a cervix carcinoma].
We present our first case of cerebral metastasis from cervical carcinoma in a living patient after primary treatment of the tumor. The metastasis was surgically removed, with a bad outcome. The lack of guidelines for the treatment of this complication, which is due to its extremely low frequency, is discussed.


Evidence of an immune-mediated mechanism for an idiosyncratic nevirapine-induced reaction in the female Brown Norway rat.
Previously, we reported a new animal model of an idiosyncratic drug reaction in which nevirapine causes a skin rash in some rats that has characteristics similar to the reaction that occurs in humans. Strong evidence that the reaction is immune-mediated was found; specifically, low-dose pretreatment induced tolerance, while with rechallenge, the time to onset decreased and the severity increased. Furthermore, splenocytes from rechallenged rats transferred rash susceptibility to naïve recipients. We now report the results of studies to explore the immune aspects of this reaction. T cells were found to play an important role, as demonstrated by their ability to adoptively transfer susceptibility to the skin reaction. Of these T cells, CD4+ cells are the likely effectors because they were capable of transferring susceptibility and the reaction was delayed in rats partially depleted of CD4+ T cells. In contrast, it appears that CD8+ T cells are not essential, as CD8+ T cells were unable to transfer sensitivity to a naïve animal and rats depleted of CD8+ T cells still developed skin rash. Unlike the penicillamine model, where we have demonstrated that the tolerance induced by low-dose treatment is immune-mediated, tolerance induced by low-dose nevirapine appears to be largely due to induction of metabolism as it can be overcome by inhibition of cytochrome P450. Pretreatment with the immunosuppressants, cyclosporine and tacrolimus, prevented the rash and even led to resolution of the rash during nevirapine treatment. These studies reinforce the hypothesis that the reaction in this model is similar to that which occurs in humans. In particular, the finding that CD4+ T cells may play a central role in this model fits with the observation that the incidence of idiosyncratic reactions to nevirapine in humans appears to be lower in patients with low CD4+ counts.


A mannitol-based buffer improves single-cell RNA sequencing of high-salt marine cells.
Single-cell RNA sequencing (scRNA-seq) enables discovery of novel cell states by transcriptomic profiling with minimal prior knowledge, making it useful for studying non-model organisms. For most marine organisms, however, cells are viable at a higher salinity than is compatible with scRNA-seq, impacting data quality and cell representation. We show that a low-salinity phosphate buffer supplemented with D-mannitol (PBS-M) enables higher-quality scRNA-seq of blood cells from the tunicate Ciona robusta. Using PBS-M reduces cell death and ambient mRNA, revealing cell states not otherwise detected. This simple protocol modification could enable or improve scRNA-seq for the majority of marine organisms.


A case report of possible health benefits of extra virgin olive oil.
The literature on the chemical analysis of cooking oils suggests that the cholesterol-reducing effect may well be due to the antioxidant agents rather than unsaturated fats. Furthermore, antioxidant agents are present in extra virgin olive oil and not in olive oil. There is some evidence, based on studies using patients, to support such a supposition. In this paper, we present a case report on the possible health effects of changing from olive oil to extra virgin olive oil. The case report is intended to raise some relevant issues to stimulate a debate and more research in this area.


Community-based aftercare following an emergency department presentation for attempted suicide or high risk for suicide: study protocol for a non-randomised controlled trial.
Suicide is a major public health issue worldwide. Those who have made a recent suicide attempt are at high risk for dying by suicide in the future, particularly during the period immediately following departure from a hospital emergency department. As such the transition from hospital-based care to the community is an important area of focus in the attempt to reduce suicide rates. There is a need for evaluation studies to test the effectiveness of interventions directed to this stage (termed 'aftercare' interventions). A controlled non-randomised two group (intervention vs treatment-as-usual control) design, using an intention-to-treat model, will evaluate the effectiveness of a suicide prevention aftercare intervention providing follow-up after presentations to a hospital emergency department as a result of a suicide attempt or high risk for suicide. The intervention is a community-based service, utilising two meetings with a mental health clinician and follow-up contacts by peer workers via a combination of face-to-face and telephone for four weeks, with the option of extension to 12 weeks. Seventy-five participants of the intervention service will be recruited to the study and compared to 1265 treatment-as-usual controls. The primary hypotheses are that over 12 months, those who participate in the aftercare follow-up intervention are less likely than controls to present to a hospital emergency department for a repeat suicide attempt or because of high risk for suicide, will have fewer re-presentations during this period and will have lower all-cause mortality. As a secondary aim, the impact of the intervention on suicide risk factors for those who participate in the service will be evaluated using pre- and post-intervention repeated measures of depression, anxiety, stress, hopelessness, belongingness, burdensomeness, and psychological distress. Enrolments into the study commenced on 1 November 2017 and are anticipated to cease in November 2019. The study aims to contribute to the understanding of effective interventions for individuals who have presented to a hospital emergency department as a result of a suicide attempt or at high risk for suicide and provide evidence in relation to interventions that incorporate peer-workers. ACTRN12618001701213 . Registered on 16 October 2018. Retrospectively registered.


Open management of complex infrarenal aortic occlusive disease.
Open aortic reconstruction for complex aortoiliac occlusive disease is a time-honored and durable solution. Symptoms manifest as disabling claudication or chronic limb threatening ischemia in patients with multilevel disease. Advanced endovascular techniques have supplanted a large volume of aortic surgery. Nonetheless, it is essential for surgeons-in-training to learn and hone their skills in open aortic surgery. Comprehensive literature review over the past 50 years was conducted on the topics of "aortic occlusive disease," "aortic bypass," and "iliofemoral bypass." Pertinent articles were selected for inclusion as references. The technical aspects of the various aortoiliac exposures are described and selected case images were chosen from the senior author's experience. This review paper details the various operative approaches to open aortoiliac revascularization with emphasis on "tips and tricks" for the learner.


Transcanal Endoscopic Ear Surgery for Congenital Cholesteatoma.
As endoscopic instrumentation, techniques and knowledges have significantly improved recently, endoscopic ear surgery has become increasingly popular. Transcanal endoscopic ear surgery (TEES) can provide better visualization of hidden areas in the middle ear cavity during congenital cholesteatoma removal. We aimed to describe outcomes for TEES for congenital cholesteatoma in a pediatric population. Twenty-five children (age, 17 months to 9 years) with congenital cholesteatoma confined to the middle ear underwent TEES by an experienced surgeon; 13 children had been classified as Potsic stage I, seven as stage II, and five as stage III. The mean follow-up period was 24 months. Recurrence of congenital cholesteatoma and surgical complication was observed. Congenital cholesteatoma can be removed successfully via transcanal endoscopic approach in all patients, and no surgical complications occurred; only one patient with a stage II cholesteatoma showed recurrence during the follow-up visit, and the patient underwent revision surgery. The other patients underwent one-stage operations and showed no cholesteatoma recurrence at their last visits. Two patients underwent second-stage ossicular reconstruction. Although the follow-up period and number of patients were limited, pediatric congenital cholesteatoma limited to the middle ear cavity could be safely and effectively removed using TEES.


Inflammatory Myopathy Associated with Anti-mitochondrial Antibody-negative Primary Biliary Cholangitis Diagnosed by a Liver Biopsy.
Anti-mitochondrial antibody (AMA)-associated myopathies represent a homogeneous disease entity with severe arrhythmia and slowly progressive proximal muscle weakness with lordotic posture, irrespective of the presence of primary biliary cholangitis (PBC). We herein report a case of myositis associated with PBC without AMAs. A 48-year-old woman presented with clinical features very similar to AMA-associated myositis, despite negative AMAs. PBC, ascertained by a liver biopsy performed based on mildly elevated liver enzymes, and the efficacy of steroid therapy on muscle weakness confirmed the diagnosis of immune-mediated myositis. When AMAs are negative, a liver biopsy is indispensable for diagnosing treatable PBC-associated myositis.


Analysis of single-strand exceptional word symmetry in the human genome: new measures.
Some previous studies suggest the extension of Chargaff's second rule (the phenomenon of symmetry in a single DNA strand) to long DNA words. However, in random sequences generated under an independent symbol model where complementary nucleotides have equal occurrence probabilities, we expect the phenomenon of symmetry to hold for any word length. In this work, we develop new statistical methods to measure the exceptional symmetry. Exceptional symmetry is a refinement of Chargaff's second parity rule that highlights the words whose frequency of occurrence is similar to that of its reversed complement but dissimilar to the frequencies of occurrence of other words which contain the same number of nucleotides A or T. We analyze words of lengths up to 12 in the complete human genome and in each chromosome separately. We assess exceptional symmetry globally, by word group, and by word. We conclude that the global symmetry present in the human genome is clearly exceptional and significant. The chromosomes present distinct exceptional symmetry profiles. There are several exceptional word groups and exceptional words with a strong exceptional symmetry.


Toward understanding the influence of soil metals and sulfate content on plant thiols.
Plants respond to increased concentrations of metals by a number of mechanisms, including chelation with phytochelatins (PCs). Soil specimens and plants (Veronica anagalis-aquatica, Typha domingensis, Cynodon dactylon, Chenopodium album, Rumex dentatus, Amaranthus gracilis, Chenopodium murale, Inula viscosa) leaves were collected from two sites in northern Jordan and subsequently metals (cadmium, copper, and lead), sulfate, and PC (from leaves) levels were determined. One of these sites was contaminated with metals and the other served as a control site. The contaminated site had elevated cadmium, copper, lead, and sulfate levels. This increase of metal and sulfate levels in the soil at the contaminated site correlated with a rise in plant total glutathione (GSH(T)) and cysteine (CYS(T)). These increases were not attributed to an elevation in total phytochelatin levels. However, a significant increase in the ratio of short-chain phytochelatins to the total phytochelatin stores was observed. The individual effects of metals and sulfate on glutathione, short-chain PCs and long-chain PCs levels were dissimilar.


Longitudinal In Vivo Changes in Retinal Ganglion Cell Dendritic Morphology After Acute and Chronic Optic Nerve Injury.
To characterize in vivo dendritic changes in retinal ganglion cells (RGCs) after acute (optic nerve transection, ONT) and chronic (experimental glaucoma, EG) optic nerve injury. ONT and EG (microbead model) were carried out in Thy1-YFP mice in which the entire RGC dendritic arbor was imaged with confocal fluorescence scanning laser ophthalmoscopy over two weeks in the ONT group and over two and six months, respectively, in two (groups 1 and 2) EG groups. Sholl analysis was used to quantify dendritic structure with the parameters: area under the curve (AUC), radius of the dendritic field, peak number of intersections (PI), and distance to the PI (PD). Dendritic changes were observed after three days post-ONT with significant decreases in all parameters at two weeks. In group 1 EG mice, mean (SD) intraocular pressure (IOP) was 15.2 (1.1) and 9.8 (0.3) mmHg in the EG and untreated contralateral eyes, respectively, with a significant corresponding decrease in AUC, PI, and PD, but not radius. In group 2 mice, the respective IOP was 13.1 (1.0) and 8.8 (0.1) mmHg, peaking at two months before trending towards baseline. Over the first two months, AUC, PI, and PD decreased significantly, with no further subsequent changes. The rates of change of the parameters after ONT was 5 to 10 times faster than in EG. Rapid dendritic changes occurred after ONT, while changes in EG were slower and associated with level of IOP increase. The earliest alterations were loss of inner neurites without change in dendritic field.


SNP imputation bias reduces effect size determination.
Imputation is a commonly used technique that exploits linkage disequilibrium to infer missing genotypes in genetic datasets, using a well-characterized reference population. While there is agreement that the reference population has to match the ethnicity of the query dataset, it is common practice to use the same reference to impute genotypes for a wide variety of phenotypes. We hypothesized that using a reference composed of samples with a different phenotype than the query dataset would introduce imputation bias. To test this hypothesis we used GWAS datasets from Amyotrophic Lateral Sclerosis (ALS), Parkinson Disease (PD), and Crohn's Disease (CD). First, we masked and then performed imputation of 100 disease-associated markers and 100 non-associated markers from each study. Two references for imputation were used in parallel: one consisting of healthy controls and another consisting of patients with the same disease. We assessed the discordance (imprecision) and bias (inaccuracy) of imputation by comparing predicted genotypes to those assayed by SNP-chip. We also assessed the bias on the observed effect size when the predicted genotypes were used in a GWAS study. When healthy controls were used as reference for imputation, a significant bias was observed, particularly in the disease-associated markers. Using cases as reference significantly attenuated this bias. For nearly all markers, the direction of the bias favored the non-risk allele. In GWAS studies of the three diseases (with healthy reference controls from the 1000 genomes as reference), the mean OR for disease-associated markers obtained by imputation was lower than that obtained using original assayed genotypes. We found that the bias is inherent to imputation as using different methods did not alter the results. In conclusion, imputation is a powerful method to predict genotypes and estimate genetic risk for GWAS. However, a careful choice of reference population is needed to minimize biases inherent to this approach.


Simvastatin profoundly impairs energy metabolism in primary human muscle cells.
Simvastatin use is associated with muscular side effects, and increased risk for type 2 diabetes (T2D). In clinical use, simvastatin is administered in inactive lipophilic lactone-form, which is then converted to active acid-form in the body. Here, we have investigated if lactone- and acid-form simvastatin differentially affect glucose metabolism and mitochondrial respiration in primary human skeletal muscle cells. Muscle cells were exposed separately to lactone- and acid-form simvastatin for 48 h. After pre-exposure, glucose uptake and glycogen synthesis were measured using radioactive tracers; insulin signalling was detected with Western blotting; and glycolysis, mitochondrial oxygen consumption and ATP production were measured with Seahorse XFe96 analyzer. Lactone-form simvastatin increased glucose uptake and glycogen synthesis, whereas acid-form simvastatin did not affect glucose uptake and decreased glycogen synthesis. Phosphorylation of insulin signalling targets Akt substrate 160 kDa (AS160) and glycogen synthase kinase 3β (GSK3β) was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. These data suggest that lactone- and acid-forms of simvastatin exhibit differential effects on non-oxidative glucose metabolism as lactone-form increases and acid-form impairs glucose storage into glycogen, suggesting impaired insulin sensitivity in response to acid-form simvastatin. Both forms profoundly impair oxidative glucose metabolism and energy production in human skeletal muscle cells. These effects may contribute to muscular side effects and risk for T2D observed with simvastatin use.


Mima polymorpha infection.
Two cases of human infection by Mima polymorpha are described. From these cases, and from the literature, it is concluded that this species is heterogeneous with respect to its biochemical properties. From comparative studies it is concluded that the genus Mima is unrelated to the genus Moraxella or to Bacterium anitratum.


Femtosecond electronic relaxation of excited metalloporphyrins in the gas phase.
A systematic study of the ultrafast decay of metalloporphyrins containing various transition metals with partially filled 3d shells and zinc (3d filled) is reported here after excitation in the second excited state of the system (Soret band). Both time-of-flight mass spectrometry and velocity map imaging have been used for detection. A general biexponential decay with a short time constant tau1 approximately 100 fs is observed for the transition metal porphyrins, followed by a tau2 approximately 1 ps time decay. This evolution is interpreted as a porphyrin-to-metal charge transfer, tau1, followed by a back transfer, tau2, which leads to an excited state (d,d*) localized on the metal. These conclusions stem from the different behaviors of zinc and the transition metal porphyrins. A porphyrin-to-metal charge transfer model is chosen to describe the relaxation mechanism, based upon the fact that transition metalloporphyrins can accept electrons on the metal site, in contrast to zinc porphyrins.


Chromosomal abnormalities and their relation to disease.
When human chromosome anomalies were first described in 1959, it appeared that specific abnormalities might be correlated with specific syndromes. Mongolism and the D and E syndromes are examples of specific syndromes associated with the presence of an extra autosome. Klinefelter's syndrome may be associated with a variety of different sex chromosome anomalies including XXY, XXYY, XXXY and XXXXY. The lastnamed variant is the only one that frequently presents features distinguishing it from the others. An XO sex chromosome complex is found in many women with gonadal dysgenesis. However, a variety of mosaicisms have been described in association with this condition, including XO/XX, XO/XXX, XO/XX/XXX, XO/XY and XO/XYY. Extra X chromosomes in phenotypical females do not seem to impair fertility or be consistently associated with congenital anomalies. Two families are described in which chromosome anomalies were found, but the association with defects was irregular. In one family the abnormality involved one of the number 16 chromosomes and in the other it involved one of the small acrocentric chromosomes.


Causal Attributions in Breast Cancer Patients Planning to Undergo Adjuvant Endocrine Therapy.
The aim of this study was to explore causal attributions among Korean breast cancer patients who were planning to undergo adjuvant endocrine therapy (AET) as well as the relationships between patient demographic and clinical characteristics and their causal attributions. Causal attributions were assessed with an open-ended response item, which asked patients to list what they thought were the three most important causal factors of their illness. The relationships between patient characteristics and causal attributions were determined through univariate analysis, and the relationships between causal attributions were obtained using social network analysis. A total of 299 participants provided 707 responses. Stress, diet, and exercise were believed to be the three most likely causes of breast cancer. There were no significant differences between causal attributions and the age, education level, marital status, or cancer stage of patients. However, there were differences in the associations between personality, genetics, and reproductive history and patient-identified causal attributions according to the patients' family history of cancer. Patients with a family history of cancer were more likely to believe that personality and genetics/family history were causes of breast cancer compared to patients without such a history. Therefore, it is necessary to educate patients to perceive stress and lifestyle-related factors as modifiable causal factors in order to have a positive effect on their adherence to AET.


The utility and durability of vein bypass grafts originating from the popliteal artery for limb salvage.
Short vein grafts originating from sites distal to the common femoral artery have been reported to be useful in selected patients with tibial artery disease. From 1987 to 1993, we performed 504 consecutive infrainguinal vein bypass grafts, of which 56 (11%) originated from the popliteal artery, 25 above and 31 below the knee. The patients were 16 women and 37 men, with a mean age of 62.4 years. Eighty-seven percent were diabetic, 57% had clinically obvious coronary artery disease, and 28% had end-stage renal disease (ESRD). The indication for surgery was ulceration or gangrene in 93% of cases. We preferentially used reversed greater saphenous vein harvested from the thigh to optimize conduit quality and avoid lower leg wound complications. The outflow artery sites were: dorsal pedal (17), posterior tibial (14), peroneal (10), anterior tibial (8), lateral or medial plantar (5), and sequential tibial (2). All patients were followed postoperatively with serial duplex surveillance. The mean follow-up was 12.5 months (range 1 to 66). In-hospital mortality was 5.4%. Mortality at 24 months was 19% overall and 38% in patients with ESRD. Limb salvage was 77% at 3 years, 92% in patients with normal renal function versus 59% in those with ESRD (P < 0.003). Primary graft patency by life-table analysis was 94% at 1 month and 84% at 3 years. Five patients with patent grafts required amputation, 4 early and 1 late. Eight months after surgery, 1 patient (1.8%) developed superficial femoral artery stenosis which was diagnosed by duplex surveillance and successfully treated by percutaneous transluminal balloon angioplasty. Vein bypass grafts originating from the popliteal artery are effective and durable. Proximal disease progression rarely poses a significant threat to long-term graft patency. Patients with ESRD, blind tibial outflow tracts, and extensive forefoot lesions appear to be at increased risk of limb loss even with continued graft patency.


Early-emerging cognitive vulnerability to depression and the serotonin transporter promoter region polymorphism.
Serotonin transporter promoter (5-HTTLPR) genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype.


Retrephination of eccentric donor graft for descemet stripping automated endothelial keratoplasty.
We describe a technique of intraoperative eccentric retrephination of Descemet stripping automated endothelial keratoplasty (DSAEK) donor graft to avoid the presence of epithelium on the graft lenticule. Trephination of the DSAEK graft may prove to be very challenging for surgeons, especially when flap diameter is small; this can result in an eccentric trephination and the presence of epithelium on the graft. Insertion of epithelium with DSAEK donor graft into the anterior chamber could result in epithelial ingrowth and downgrowth, complications that may lead to poor visual outcomes, graft detachment, and anterior chamber angle closure. A second eccentric retrephination is a simple and easy-to-perform intraoperative surgical step that could avoid the presence of corneal epithelium on the DSAEK donor graft.


Heavy ion and X-ray irradiation alter the cytoskeleton and cytomechanics of cortical neurons.
Heavy ion beams with high linear energy transfer exhibit more beneficial physical and biological performance than conventional X-rays, thus improving the potential of this type of radiotherapy in the treatment of cancer. However, these two radiotherapy modalities both cause inevitable brain injury. The objective of this study was to evaluate the effects of heavy ion and X-ray irradiation on the cytoskeleton and cytomechanical properties of rat cortical neurons, as well as to determine the potential mechanism of neuronal injury after irradiation. Cortical neurons from 30 new-born mice were irradiated with heavy ion beams at a single dose of 2 Gy and X-rays at a single dose of 4 Gy; subsequent evaluation of their effects were carried out at 24 hours after irradiation. An immunofluorescence assay showed that after irradiation with both the heavy ion beam and X-rays, the number of primary neurons was significantly decreased, and there was evidence of apoptosis. Radiation-induced neuronal injury was more apparent after X-irradiation. Under atomic force microscopy, the neuronal membrane appeared rough and neuronal rigidity had increased. These cell changes were more apparent following exposure to X-rays. Our findings indicated that damage caused by heavy ion and X-ray irradiation resulted in the structural distortion and rearrangement of the cytoskeleton, and affected the cytomechanical properties of the cortical neurons. Moreover, this radiation injury to normal neurons was much severer after irradiation with X-rays than after heavy ion beam irradiation.


[Uncommon localization of osteomyelitis].
Group A beta-hemolytic streptococcus (GAS) causes almost 10% of acute hematogenous osteomyelitis (AHOM). These entities are frequently located in long bones (femur, tibia and humerus), and only 6-8% of all AHOM are located in the pelvis. This uncommon localization delays diagnosis and can lead to inappropriate management, with negative effects on outcomes. We present the case of a 6-year-old boy with high fever, pain in the right hip and difficulty in walking due to pelvic AHOM and septic shock caused by GAS. We also provide a review of the literature.


Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development.
Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development. Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF) - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development. This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.


The discriminative ability and diagnostic utility of the ADOS-G, ADI-R, and GARS for children in a clinical setting.
Recent years have seen a surge of interest in assessment instruments for diagnosing autism in children. Instruments have generally been developed and evaluated from a research perspective. The Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and Gilliam Autism Rating Scale (GARS) have received considerable attention and are widely used. The objective of this study was to explore the diagnostic utility and discriminative ability of these tools using a clinical population of children referred to a specialty diagnostic clinic over a 3 year time span. The results indicated that the ADOS-G and ADI-R led to approximately 75 percent agreement with team diagnoses, with most inconsistencies being false positive diagnoses based on the measures. The GARS was generally ineffective at discriminating between children with various team diagnoses and consistently underestimated the likelihood of autism. The findings have important implications for the use of these measures in both research and clinical practice.


Validity and Reliability of Facial Rating of Perceived Exertion Scales for Training Load Monitoring.
van der Zwaard, S, Hooft Graafland, F, van Middelkoop, C, and Lintmeijer, LL. Validity and reliability of facial rating of perceived exertion scales for training load monitoring. J Strength Cond Res 37(5): e317-e324, 2023-Rating of perceived exertion (RPE) is often used by coaches and athletes to indicate exercise intensity, which facilitates training load monitoring and prescription. Although RPE is typically measured using the Borg's category-ratio 10-point scale (CR10), digital sports platforms have recently started to incorporate facial RPE scales, which potentially have a better user experience. The aim of this study was to evaluate the validity and reliability of a 5-point facial RPE scale (FCR5) and a 10-point facial RPE scale (FCR10), using the CR10 as a golden standard and to assess their use for training load monitoring. Forty-nine subjects were grouped into 17 untrained (UT), 19 recreationally trained (RT), and 13 trained (T) individuals Subjects completed 9 randomly ordered home-based workout sessions (3 intensities × 3 RPE scales) on the Fitchannel.com platform. Heart rate was monitored throughout the workouts. Subjects performed 3 additional workouts to assess reliability. Validity and reliability of both facial RPE scales were low in UT subjects (intraclass correlation [ICC] ≤ 0.44, p ≤ 0.06 and ICC ≤ 0.43, p ≥ 0.09). In RT and T subjects, validity was moderate for FCR5 (ICC ≥ 0.72, p < 0.001) and good for FCR10 (ICC ≥ 0.80, p < 0.001). Reliability for these groups was rather poor for FCR5 (ICC = 0.51, p = 0.006) and moderate for FCR10 (ICC = 0.74, p < 0.001), but it was excellent for CR10 (ICC = 0.92, p < 0.001). In RT and T subjects, session RPE scores were also strongly related to Edward's training impulse scores ( r ≥ 0.70, p < 0.001). User experience was best supported by the FCR10 scale. In conclusion, researchers, coaches, strength and conditioning professionals, and digital sports platforms are encouraged to incorporate the valid and reliable FCR10 and not FCR5 to assess perceived exertion and internal training load of recreationally trained and trained individuals.


Microbial resistance to metals in the environment.
Many microorganisms demonstrate resistance to metals in water, soil and industrial waste. Genes located on chromosomes, plasmids, or transposons encode specific resistance to a variety of metal ions. Some metals, such as cobalt, copper, nickel, serve as micronutrients and are used for redox processes, to stabilize molecules through electrostatic interactions, as components of various enzymes, and for regulation of osmotic pressure. Most metals are nonessential, have no nutrient value, and are potentially toxic to microorganisms. These toxic metals interact with essential cellular components through covalent and ionic bonding. At high levels, both essential and nonessential metals can damage cell membranes, alter enzyme specificity, disrupt cellular functions, and damage the structure of DNA. Microorganisms have adapted to the presence of both nutrient and nonessential metals by developing a variety of resistance mechanisms. Six metal resistance mechanisms exist: exclusion by permeability barrier, intra- and extra-cellular sequestration, active transport efflux pumps, enzymatic detoxification, and reduction in the sensitivity of cellular targets to metal ions. The understanding of how microorganisms resist metals can provide insight into strategies for their detoxification or removal from the environment.


Tracking of blood pressure from childhood to adolescence in a Greek cohort.
Studies have reported tracking of blood pressure (BP) from childhood to adulthood but with inconsistent results mainly due to methodological and ethnic differences. We aimed to examine BP tracking during a 7-year period in a Greek cohort. This is a longitudinal school-based study conducted during 1990-96 in Athens, Greece. Children underwent BP and anthropometric measurements on two to three visits annually (averaged to annual values) for 7 years. A total of 166 children with complete yearly follow-up data for the examined period were included (mean baseline age 9 ± 1.7 years, range: 5-12 years, 89 boys). At baseline, the prevalence of pre- and hypertension was 22.9 and 24.1% respectively and at the end of the follow-up 24.1% (P = NS vs. baseline) and 13.3% (P = 0.02 vs. baseline) respectively. Systolic/diastolic BP tracking correlation coefficients between 1990 and 1996 were 0.38 (P < 0.001)/0.20 (P = 0.06) for boys and 0.30 (P = 0.007)/0.22 (P = 0.06) for girls. Among children with baseline BP ≥90th centile (systolic and/or diastolic), 44% remained in the same BP range after 7 years. In stepwise multiple regression analysis, baseline systolic BP, male gender, baseline body mass index (BMI) and change in BMI from baseline to the end of the follow-up (ΔBMI) were significant predictors of systolic BP levels at the end of the follow-up. Baseline diastolic BP, baseline BMI and ΔBMI were significant predictors of diastolic BP at the end of the follow-up. These data suggest that the risk of developing high BP during adolescence can be predicted by BP and BMI at childhood.


The minnow Phoxinus lumaireul (Leuciscidae) shifts the Adriatic-Black Sea basin divide in the north-western Dinaric Karst region.
Karst landscapes are characterized by intermittent and sinking streams. The most common method used to study underground hydrological connections in karst is tracing tests. However, a more biologically oriented approach has been suggested: analysis of the genetic structure of aquatic organisms. Biological tracers can be sought among trogloxenes, that is, surface species that occasionally enter caves and groundwater. One such example is the fish genus Phoxinus, which exhibits high genetic diversity and complex phylogeography in the Balkan Peninsula. In the north-western Dinaric Karst, the complex hydrological network was digitalized in 2020. Contemporaneously, Phoxinus lumaireul populations in the Slovenian Dinaric Karst were intensively sampled and analysed for fragments of two mitochondrial genes and one nuclear gene. The derived phylogeographic structure and data on hydrological connections were compared to evaluate support for three alternative scenarios: The genetic structure (1) is a consequence of the ongoing geneflow through underground connections, (2) reflects a previous hydrological network or (3) is an outcome of anthropogenic translocations. The results suggest that the first two scenarios seem to have played a major role, while the third has not had profound effects on the genetic composition. Comparison between the genetic structure of Slovenian Dinaric Karst sampling sites and that of hydrologically isolated reference sampling sites indicated a greater genetic connectivity in the former. Moreover, the range of Adriatic (1a) and Black Sea (1c) haplotypes does not correspond to the Adriatic-Black Sea basin divide but is shifted northwards.


A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger mediated ring-closure.
Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing α-, β- or γ-amino acid residues is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and tripeptides--recognized as difficult targets--were obtained in moderate to good yields according to a straightforward sequence. Empirical force-field calculations were undertaken to determine their conformational behaviors and showed high levels of similarity with X-ray results. A computational study at the B3LYP/6-31+G** level of theory afforded information regarding the impact of the sequence, ring-size and substitution on the activation barriers for the cyclization of azido peptide thioesters.


Akkermansia muciniphila can reduce the damage of gluco/lipotoxicity, oxidative stress and inflammation, and normalize intestine microbiota in streptozotocin-induced diabetic rats.
This study aimed to investigate how Akkermansia muciniphila can implicate type 2 diabetes mellitus and the mechanisms underlying the effects A. muciniphila on type 2 diabetes mellitus. Normal and streptozotocin-induced diabetic Sprague-Dawley rats were orally administered with A. muciniphila and solvent. After 4 weeks of treatment, diabetic rats orally administered with live or pasteurized A. muciniphila exhibited significant increase in the blood concentration of high-density lipoprotein, and decrease in the hepatic glycogen, serum plasminogen activator inhibitor-1, tumor necrosis factor-α, lipopolysaccharide, malondialdehyde and total glucagon-like peptide-1. Moreover, diabetic rats orally administered with A. muciniphila showed significantly increased species alpha diversity and gene function in gut microbes. These results indicated that A. muciniphila can improve liver function, reduce gluco/lipotoxicity, alleviate oxidative stress, suppress inflammation and normalize intestine microbiota of the host animal, thereby ameliorating type 2 diabetes mellitus. Akkermansia muciniphila might be considered as one of the ideal new probiotics used in the management of type 2 diabetes mellitus in future.


Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study.
Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma. This study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations. We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls. This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.


Methicillin resistant Staphylococcus aureus infections following cardiac surgery: incidence, impact and identifying adverse outcome traits.
To assess the incidence and impact of Methicillin-resistant Staphylococcus aureus (MRSA) infections on cardiac surgery outcomes and to identify adverse outcome traits. Retrospective analysis of prospectively collected data from cardiac surgical and microbiology databases between April 2000 and March 2005. The overall and yearly incidence of positive MRSA cultures was examined along with the distribution of clinical infections and the associated mortality. Pre-operative patient characteristics were analysed between non-survivors and survivors of MRSA infections. Multivariate logistic regression was used to assess the relationship between pre-operative patient characteristics and in-hospital mortality in patients with MRSA. A comparison of post-operative outcomes between non-survivors and survivors of MRSA infections was also carried out and included in the logistic regression analysis. There were 319 patients with positive MRSA cultures during the study period with an overall incidence of 3.9%. Yearly incidence ranged from 2.4% to 5.2%. There were 120 carriers with pre-operative positive cultures of which 25 developed clinical surgical infections leaving 224 patients as the study group. Overall mortality in patients with MRSA during the study period was 12.9%(41/319). Mortality in the study group was 17.8% (40/224). Mortality comparison between MRSA and non-MRSA mediastinitis was 26.7%(8/30) and 17.1%(13/76), respectively (p=0.26). Mortality between MRSA and non-MRSA septicaemia was 46.9% (15/32) and 52.9% (37/70) (p=0.57). Applying the logistic EuroSCORE to the MRSA patients revealed that non-survivors had a significantly higher pre-operative risk of 10.4% compared to survivors with a pre-operative risk of 6.2% (p=0.003). Renal dysfunction and poor ejection fraction were found to be pre-operative factors associated with mortality in MRSA patients following the multivariate logistic regression analysis. Non-survivors had longer stays on intensive care, longer ventilation times, and were more likely to require support with balloon pumps and haemofiltration. MRSA septicaemia and length of ventilation were significantly associated with mortality in MRSA patients ahead of pre-operative characteristics. The incidence of MRSA is low, but carries a high mortality. MRSA septicaemia and mediastinitis have the highest associated mortality; however, this is not significantly different from non-MRSA infections. Patients with MRSA who die have higher pre-operative risk and have a poorer post-operative course than survivors.


Intrafascicular recordings of afferent multi-unit activity from the human supraorbital nerve.
Intrafascicular recordings of afferent multi-unit activity were obtained from the supraorbital nerve in 40 healthy human volunteers, using tungsten micro-electrodes inserted percutaneously at the eyebrow. Seventy-seven fascicular receptive fields were mapped; their area ranged from 2 to 76 cm2, with a median of 19 cm2. The smallest fields were found in the eyebrow region, and the largest on the scalp. In response to non-painful electrical intradermal stimulation, the conduction velocity of the fastest nerve fibres was calculated to be 40 +/- 2 m s-1 (mean +/- SEM), and the later part of the afferent volley corresponded to a velocity of 20 +/- 1 m s-1. The responses to skin indentation indicated that the density of mechanoreceptive innervation was higher in the lower part of the forehead than in the upper/posterior part of the innervation territory of the nerve. A rapid mechanical tap on the forehead and scalp evoked two major afferent volleys corresponding to the on- and off-phase of the stimulus. Manipulation of hairs resulted not only in dynamic responses to hair movement, but also in a static discharge during sustained hair displacement. When a fascicular field included the eyebrow region, skin stretching during blinking movements evoked distinct afferent activity. Following mechanical and electrical stimuli there were no signs of 'trigeminal antidromic potentials' of the type described in the cat and monkey.


[Twin gestation with regressive partial hydatidiform mole and coexisting live fetus].
The case of dichorionic twin pregnancy is described, with a fused placenta, one part of which is represented by a tissue of partial hydatidiform mole (PHM) with signs of regression, the second part is a placenta of a common structure with a normal development of the second twin. The delivery took place at the term of 38 weeks with a live healthy girl weighing 3250 g. A single placental disc consisted of two fused placentas with a clear boundary between them. The placenta of a live-born girl was mature, with focal chorangiosis, the second part of the disc was represented by the PHM tissue with avascular giant bizarre villi, some of them with central cisterns, with stromal fibrosis, low proliferative activity of the villous trophoblast and a significant narrowing of the intervillous space. A genetic study was carried out on the material of paraffin blocks from two parts of the placental disc containing the tissue of the villous chorion, and the blood of the parents. Comparative analysis of DNA isolated from the paraffin block of PHM with the DNA of the parents revealed the presence of diandric dispermic triploidy. No chromosomal pathology was found in the placenta of a living girl. For hydatidiform mole in the case of multiple pregnancy, an increase in the volume of the affected placenta is characteristic compared to the normal placenta of the twin. In our observation, the presence in the placenta with PHM signs characteristic of placentas with antenatal fetal death, stromal fibrosis of the villi and low proliferative activity of the trophoblast suggests a regression of PHM.


Controlling Nucleation in Quasi-Two-Dimensional Langmuir Poly(l-lactide) Films through Variation of the Rate of Compression.
We studied morphological changes in a quasi-two-dimensional Langmuir film of low molar mass poly(l-lactide) upon increasing the surface density, starting from randomly distributed molecules to a homogeneous monolayer of closely packed molecules, followed by nucleation and growth of mesoscopic, three-dimensional clusters from an overcompressed monolayer. The corresponding nucleation density of mesoscopic clusters within the monolayer can be tailored through variation of the rate of compression. For a given surface density and temperature, the nucleation probability was found to increase linearly with the rate of compression, allowing to adjust the density of mesoscopic clusters over nearly 2 orders of magnitude.