FNAC study of giant cell tumor of tendon sheath (localized tenosynovial giant cell tumor): Clinico-radiological correlation and cytopathological features.
Localized tenosynovial giant cell tumor (GCT) or giant cell tumor of tendon sheath (GCTTS), is a benign nodular lesion that arises from the synovium of the tendon sheath of the hands and foot. GCTTS is characterized by the presence of multinucleated giant cells and proliferation of synovial-like mononuclear cells. A clinical diagnosis of GCTTS is kept as a differential when a firm, nodular mass shows decreased signal intensity on both T1-and T2-weighted MR imaging. Treatment is usually marginal excision of the mass. It is a retrospective study, observed in the past 3 years at a tertiary care hospital. Those cases were included in the study in which histopathological confirmation was available or if clinico-radiological features were confirmatory of the diagnosis of GCTTS when correlated with cytological features. There was a total of 24 cases, out of which 16 were females and 8 males. The tumor was located in the upper limb in 21 cases and in 3 cases the tumor was present in the lower limb. In the upper limb, 18 cases were on the right side and three cases were on the left side. In the lower limb, 1 case was present on the left and 2 on the right side. The cytomorphology consisted of mononuclear stromal cells, multinucleated giant cells, and hemosiderin-laden macrophages in variable numbers. It is important to accurately diagnose and categorize giant cell-containing lesions because their prognosis depends on the exact categorization of the tumor.


Utilization of evidence-based therapies for heart failure in the institutionalized elderly.
Heart failure (HF) is a major source of morbidity and mortality in elderly populations. A significant proportion of the elderly with HF are living in long-term care facilities. Little is known about their management. The aim of this study was to evaluate the use of evidence-based therapies in institutionalized elderly patients with HF. Retrospective chart review conducted at 15 long-term care facilities in the Capital Health Region (Edmonton, Alberta). Residents > or =65 years of age with HF were identified using a pharmacy database. Overall prevalence of HF was 15% (313/2062 residents). Mean age was 87 years, median duration of residence was 1.8 years. Utilization of ACE-inhibitors, beta-blockers and spironolactone was 51%, 16% and 10%, respectively. Use of these medications was not significantly different between subgroups of those with and without contraindications to the therapies, different advance directive levels, gender or age. Sodium and fluid restricted diets were prescribed in only 11.0% and 3.8% of residents. Weight was not regularly monitored. Influenza and pneumococcal vaccination were administered to 60.4% and 81.2% of the residents. The use of evidence-based therapies in institutionalized elderly patients with HF is low, and unexplained by contraindications or advance directives. Efforts to increase the utilization of evidence-based therapies and improve monitoring are warranted.


Structure of subcomplex Iβ of mammalian respiratory complex I leads to new supernumerary subunit assignments.
Mitochondrial complex I (proton-pumping NADH:ubiquinone oxidoreductase) is an essential respiratory enzyme. Mammalian complex I contains 45 subunits: 14 conserved "core" subunits and 31 "supernumerary" subunits. The structure of Bos taurus complex I, determined to 5-Å resolution by electron cryomicroscopy, described the structure of the mammalian core enzyme and allowed the assignment of 14 supernumerary subunits. Here, we describe the 6.8-Å resolution X-ray crystallography structure of subcomplex Iβ, a large portion of the membrane domain of B. taurus complex I that contains two core subunits and a cohort of supernumerary subunits. By comparing the structures and composition of subcomplex Iβ and complex I, supported by comparisons with Yarrowia lipolytica complex I, we propose assignments for eight further supernumerary subunits in the structure. Our new assignments include two CHCH-domain containing subunits that contain disulfide bridges between CX9C motifs; they are processed by the Mia40 oxidative-folding pathway in the intermembrane space and probably stabilize the membrane domain. We also assign subunit B22, an LYR protein, to the matrix face of the membrane domain. We reveal that subunit B22 anchors an acyl carrier protein (ACP) to the complex, replicating the LYR protein-ACP structural module that was identified previously in the hydrophilic domain. Thus, we significantly extend knowledge of how the mammalian supernumerary subunits are arranged around the core enzyme, and provide insights into their roles in biogenesis and regulation.


Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate.
In androgenized-hypophysectomized rats, ovine prolactin stimulated the activity of the ornithine decarboxylase (ODC) of the lateral lobes, but not the ventral and dorsal lobes of the prostate glands in a time- and dose-dependent fashion. High degrees of enzyme stimulation were associated with significant elevations in the endogenous levels of its product, putrescine. The relative response to prolactin over basal activities was relatively unaffected by indomethacin but decreased with cycloheximide, suggesting that prostaglandins do not mediate the effects of the hormone, but that a high rate of protein synthesis is a prerequisite for its expression. Indomethacin alone significantly increased the basal activity of the enzyme above control levels, suggesting that prostaglandins may normally exert a degree of inhibition on the ODC. The selective activation of the lateral lobe ODC supports previous reports of a differential response of the various prostatic lobes to prolactin, and also provides a convenient biochemical response for examining details of prolactin action on this organ.


Prisons and the pandemic: the panopticon plays out.
Fearing the spread of the COVID 19 infection in prisons, governments have released seemingly large numbers of prisoners in many countries. However, in terms of overall percentages, the releases have been less significant. In India, prisons are overcrowded with nearly 70% under trials. With very poor sanitation and healthcare facilities, there are numerous deaths in custody due to various illnesses, including heart, lung, liver and kidney-related ailments as well as HIV, tuberculosis and cancer. It is in this context that the need to take urgent steps to contain the spread of the contagion inside prisons became apparent to the prison authorities around the time the national lockdown was announced by the Government of India. Some of the measures taken by prison departments include creation of temporary prisons to admit new prisoners and keep them in quarantine for 14 days before transferring them to the regular prisons, transfer of prisoners from congested prisons to less crowded prisons, making prisoners aware of the virus, setting up Corona care centres inside or outside prisons, etc. While prison authorities claim that they were taking necessary preventive steps within existing limitations, there has been some criticism of the inadequacy of these measures and the conditions inside prisons. The Supreme Court of India took suo moto cognizance of the issue and asked state governments to constitute a High Powered Committees to identify categories of prisoners who could be released. The article highlights that the criteria for release was based on the purported seriousness of the offence rather than vulnerability to getting infected. Also, the absence of gender disaggregated data on release of prisoners indicates the lack of importance given to the needs of women prisoners. It can be said that the policies and measures taken towards preventing the spread of COVID 19 pandemic in prisons has reinforced existing biases against prisoners. The major concern of the prison and judicial authorities was to somehow manage the situation without disturbing the 'dangerousness' and risk to 'law and order' narrative about prisoners. The article concludes by drawing attention to the fact that the Foucauldian principles of segregation, segmentation and surveillance were maintained in the decision making processes relating to treatment of prisoners during the pandemic.


Assessment of an rDNA probe filter hybridization assay for the detection of Rift Valley fever virus RNA in human serum samples from the Mauritanian epidemic.
The Rift Valley fever virus (RVFV) epidemic that occurred in southern Mauritania during the 1987 rainy season provided a unique opportunity to test and evaluate a recently developed, M-segment-specific, nucleic acid filter hybridization assay on a large collection of infected human serum samples. It afforded the opportunity to compare the procedure with two other methods for detecting virus: virus isolation and antigen detection by ELISA. The filter hybridization procedure employed a polyethylene-glycol-precipitation and proteinase-K-digestion sample treatment step developed specifically for preparing serum samples for hybridization. The procedure was less sensitive for detecting RVFV in the Mauritanian human viremic samples than in sera from experimentally infected monkeys used to evaluate this procedure. It was also less sensitive than an antigen detection procedure used to test the Mauritanian samples. However, we were able to detect virus RNA in a significant proportion of the virus-isolation-positive samples. Advances in sample preparation, labelling and detection procedures, and hybridization methods will improve the sensitivity, precision and ease of use of this assay and increase its value as a diagnostic tool.


Immediate and long-term results of percutaneous mitral balloon valvotomy in asymptomatic or minimally symptomatic patients with severe mitral stenosis.
The purpose of this study was to evaluate the safety and value of percutaneous mitral balloon valvotomy (PMBV) in asymptomatic or minimally symptomatic patients with severe mitral stenosis (MS). There are very limited data supporting the concept of PMBV in asymptomatic or minimally symptomatic patients with severe MS. We analyzed the results of 539 consecutive patients with severe MS who underwent PMBV at our hospital. Patients were divided according to their symptoms at the time of PMBV into group A (55 patients), who had few or no symptom (NYHA class 1 or 2), and group B (484 patients), who had severe symptom (NYHA class 3 or 4). Patients had clinical and echocardiographic follow-up for 0.5-15 years. There was no significant difference in baseline characteristics between the two groups. The immediate mitral valve area (MVA) was equal in both groups. The follow-up MVA was larger in group A (1.9 +/- 0.38 vs. 1.7 +/- 0.4 cm(2); P = 0.002), and restenosis occurred in 11% in group A vs. 23% in group B (P = 0.023). Actuarial freedoms from restenosis at 5, 10, and 13 years were significantly higher for group A than for group B (97% +/- 2%, 77% +/- 9%, 77% +/- 9% vs. 85% +/- 1%, 62% +/- 3%, 39% +/- 5%; P = 0.0018). Atrial fibrillation at follow-up was encountered in 11% in group A vs. 20% in group B (P = 0.042). There was a significant reduction of the left atrial size in both groups. Event-free survivals at 5, 10, and 13 years were higher for group A than for group B (97% +/- 2%, 80% +/- 9%, 80% +/- 9% vs. 86% +/- 1%, 65% +/- 3%, 42% +/- 3%; P = 0.0018). This study demonstrated excellent immediate results of PMBV in asymptomatic or minimally symptomatic patients with severe MS and long-term results are better compared to the reported natural history of such patients. We recommend mitral balloon valvotomy (MBV) for patients with severe MS with few or no symptoms, provided the valve morphology is suitable for MBV.


Genetic factors, perceived chronic stress, and the free cortisol response to awakening.
Recent studies have demonstrated that the free cortisol response to awakening can serve as a useful index of hypothalamus-pituitary-adrenal axis (HPA) activity. This endocrine marker is rather consistent, shows good intraindividual stability across time and appears to be able to uncover subtle changes in HPA regulation. The present twin study investigated genetic factors as sources of the interindividual variation of the cortisol awakening response. Furthermore, the relationship between psychological variables and morning cortisol levels was studied. On two consecutive days saliva samples were collected 0, 30, 45 and 60 minutes after awakening in 52 monozygotic and 52 dizygotic twin pairs. Moreover, samples were obtained at 0800, 1100, 1500 and 2000 h. ('short day-time profile'). Additionally, the participants filled out questionnaires assessing chronic stress load, self-esteem and self-efficacy.Heritability estimates of h(2)=0.40 for the mean increase and of h(2)=0.48 for the area under the response curve indicate a significant impact of genetic factors on cortisol levels after awakening. However, no genetic influence on the short day-time profile could be observed. Furthermore, several aspects of perceived chronic stress, namely 'worries', 'social stress' and 'lack of social recognition' were significantly associated with the awakening cortisol response. The evidence for a medium-sized, yet distinct genetic influence on cortisol levels after awakening is discussed with regard to a potential clinical relevance of genetic determinants of HPA (re)activity. In line with several recent studies, the present findings further support the view that the cortisol awakening responses is consistently enhanced under chronic stress conditions.


The cancer pain experience of Israeli and American patients 65 years and older.
With the aging of the world's population, cancer pain will become an increasingly important health issue. The purpose of this study was to describe the cancer pain experience of Americans (n = 60) and Israelis (n = 39) 65 years and older. Outpatients in teaching hospitals in the U.S. and in Israel completed study questionnaires. Thirty percent of the total variance of worst pain was explained by age, symptom severity, and cancer stage, and 40% of the total variance of pain interference was explained by whether they were American or Israeli, symptom severity, and sense of coherence. Israeli patients had significantly higher scores on worst pain and pain interference, and significantly lower pain management index (PMI) and knowledge and attitudes toward pain and pain control scores. Studies with larger samples and across different cultures are needed to confirm these findings in order to develop culturally appropriate interventions.


Mycoplasma pneumonia and atypical acute hemorrhagic edema of infancy.
Acute hemorrhagic edema of infancy is a benign rare presentation of leukocytoclastic vasculitis that affects children between 4 and 24 months of age. It usually involves the distal extremities, face, and ears. We report an atypical presentation of AHEI in a 1 year 5 months old boy starting initially over the trunk and back, then spreading to the face and extremities. Mycoplasma pneumonia IgM was found to be positive. The rash resolved spontaneously within two weeks. Herein we present a case of Mycoplasma induced AHEI with an atypical clinical presentation followed by a review of the literature.


Synthesis and cytotoxic activity of new acridine-thiazolidine derivatives.
Although their exact role in controlling tumour growth and apoptosis in humans remains undefined, acridine and thiazolidine compounds have been shown to act as tumour suppressors in most cancers. Based on this finding, a series of novel hybrid 5-acridin-9-ylmethylene-3-benzyl-thiazolidine-2,4-diones were synthesised via N-alkylation and Michael reaction. The cell viability was analysed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and DNA interaction assays were performed using electrochemical techniques.


Mechanisms underlying the formation of the amygdalar fear memory trace: A computational perspective.
Recent experimental and modeling studies on the lateral amygdala (LA) have implicated intrinsic excitability and competitive synaptic interactions among principal neurons (PNs) in the formation of auditory fear memories. The present modeling studies, conducted over an expanded range of intrinsic excitability in the network, revealed that only excitable PNs that received tone inputs participate in the competition. Strikingly, the number of model PNs integrated into the fear memory trace remained constant despite the much larger range considered, and model runs highlighted several conditioning-induced tone responsive characteristics of the various PN populations. Furthermore, these studies showed that although excitation was important, disynaptic inhibition among PNs is the dominant mechanism that keeps the number of plastic PNs stable despite large variations in the network's excitability. Finally, we found that the overall level of inhibition in the model network determines the number of projection cells integrated into the fear memory trace.


Specific phosphorylation of a COOH-terminal site on the full-length form of the alpha 1 subunit of the skeletal muscle calcium channel by cAMP-dependent protein kinase.
The primary (alpha 1) subunit of purified skeletal muscle dihydropyridine-sensitive calcium channels is present in full-length (212 kDa) and truncated (190 kDa) forms which are both phosphorylated by cAMP-dependent protein kinase (cA-PK) in vitro. In the present study, phosphorylation of the purified calcium channel by cA-PK followed by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and two-dimensional phosphopeptide mapping revealed differential phosphorylation of the related 190- and 212-kDa forms. The 190-kDa form of the alpha 1 subunit was phosphorylated on three major and three minor tryptic phosphopeptides; the 212-kDa form was phosphorylated on all six of these phosphopeptides plus two that were unique. Time course experiments showed that a single site on the COOH-terminal portion of the full-length form of the alpha 1 subunit is most intensely and rapidly (within 10 s) phosphorylated. Phosphorylation occurs almost exclusively on this COOH-terminal site unless harsh conditions such as treatment with denaturing detergents are employed to expose phosphorylation sites within the 190-kDa segment of the molecule. Elution of phosphopeptides from the second dimension chromatograph followed by immunoprecipitation with an anti-peptide antibody (anti-CP1) directed against the COOH-terminal amino acid sequence enabled us to identify this major phosphorylation site as serine 1854. The nearby consensus sites for cA-PK phosphorylation at serines 1757 and 1772 were phosphorylated only after denaturation or proteolytic cleavage. Phosphorylation of serine 1854 may play a pivotal role in the regulation of calcium channel function by cA-PK.


Reye syndrome associated with vaccination with live virus vaccines. An exploration of possible etiologic relationships.
To determine whether vaccination with live virus vaccines may be etiologically related to Reye syndrome, we examined 404 cases reported to the Center for Disease Control. Fifteen of 269 children with Reye syndrome has been inoculated with live virus vaccines within 30 days before onset of illness. Although this temporal relationship may have occurred by chance, seasonal distribution and clustering of incubation periods suggests that live virus vaccines may occasionally serve as cofactors in the etiology of Reye syndrome through undefined mechanisms.


Adults' Orientation of Children--And Children's Initiative to Pitch In--To Everyday Adult Activities in a Tsotsil Maya Community.
This chapter examines how 2-year-old children attempt to actively participate in adult work in a Mayan community in Chiapas, Mexico, and how adults contribute and accommodate to the contributions. As children enter into activities and adults orient and reorient the activity to direct the children, teaching from expert to novice is generated by children's agency in co-participatory interactions. The chapter enriches the LOPI model by focusing on the structure of participation and communication, social and community organization, and the evaluation that occurs in the activity itself.


Functional diversity of complex I subunits in Candida albicans mitochondria.
Our interest in the mitochondria of Candida albicans has progressed to the identification of several proteins that are critical to complex I (CI) activity. We speculated that there should be major functional differences at the protein level between mammalian and fungal mitochondria CI. In our pursuit of this idea, we were helped by published data of CI subunit proteins from a broad diversity of species that included two subunit proteins that are not found in mammals. These subunit proteins have been designated as Nuo1p and Nuo2p (NADH-ubiquinone oxidoreductases). Since functional assignments of both C. albicans proteins were unknown, other than having a putative NADH-oxidoreductase activity, we constructed knock-out strains that could be compared to parental cells. The relevance of our research relates to the critical roles of both proteins in cell biology and pathogenesis and their absence in mammals. These features suggest they may be exploited in antifungal drug discovery. Initially, we characterized Goa1p that apparently regulates CI activity but is not a CI subunit protein. We have used the goa1∆ for comparisons to Nuo1p and Nuo2p. We have demonstrated the critical role of these proteins in maintaining CI activities, virulence, and prolonging life span. More recently, transcriptional profiling of the three mutants and an ndh51∆ (protein is a highly conserved CI subunit) has revealed that there are overlapping yet also different functional assignments that suggest subunit specificity. The differences and similarities of each are described below along with our hypotheses to explain these data. Our conclusion and perspective is that the C. albicans CI subunit proteins are highly conserved except for two that define non-mammalian functions.


Leptin and steroid hormone responses to exercise in adolescent female runners over a 7-week season.
The purpose of the study was to investigate the responses of leptin and steroid hormones to maximal exercise in adolescent female runners over a competitive season. Seven adolescent female distance runners completed three testing trials during weeks 1.4 and 7 of their high-school track season. Blood samples were collected before and after a discontinuous graded exercise test to exhaustion (GXT) for each trial. Tests were administered during the subjects' normal training time (3:30 p.m.-5:00 p.m.). Compared to week 1, peak O2 uptake rose significantly during the season and was 10% and 7% higher at weeks 4 and 7, respectively. Levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisol, testosterone, and leptin increased significantly in response to the graded exercise tests. Testosterone levels were also changed over the course of the study. Resting testosterone levels and testosterone responses to exercise in weeks 4 and 7 were both higher than in week 1. Resting concentrations and acute increases of the other hormones were not changed over the season. It appears, therefore, that DHEA, DHEAS, cortisol, testosterone and leptin concentrations increase in response to running in adolescent female runners. Data also suggest that training and/or maturation increases resting testosterone concentrations and testosterone responses to running in adolescent female runners during a training season.


Nonoperative management of acute spontaneous renal artery dissection.
Isolated spontaneous renal artery dissection is a rare condition that can result in renal parenchymal loss and severe hypertension. Although several risk factors have been identified in association with renal artery dissection, the natural history is not well defined. The rarity and nonspecific presentation of the disease often lead to diagnostic delay. That, coupled with the anatomic limitations imposed by dissection into small branch arteries, frequently precludes successful revascularization. Over a 12-month period, four cases of spontaneous renal artery dissection (SRAD) were treated at a single institution. The patients (ages 44-58 years) presented with acute onset of abdominal/flank pain, fever, and hematuria. Diagnostic work-up included an abdominal CT scan revealing segmental renal infarction. Angiographic evaluation was diagnostic for renal artery dissection in all cases. In one case there was evidence of fibromuscular dysplasia (FMD), and in a second there was acute dissection superimposed upon atherosclerotic disease. Diagnosis was made within 12-72 hr of the onset of symptoms. All patients were managed expectantly with anticoagulation. Two patients were known to have a history of hypertension prior to admission. All four patients have required antihypertensive treatment following dissection, but the condition has been easily controlled. Renal function has remained stable in all cases. None of the four cases required exploration. Two of the four patients underwent repeat angiographic evaluation for recurrent symptoms of pain. In the case of the patient with FMD, a new dissection was seen in the contralateral renal artery, and in the second, repeat angiogram revealed proximal remodeling of the dissected artery. Management strategies for SRAD include surgical revascularization, endovascular intervention, and observation with or without anticoagulation. The available literature does not demonstrate a clear benefit of treatment with any of these modalities. In the short term, the combination of anticoagulation and expectant management appears to produce satisfactory outcomes for this difficult problem.


Sex disparity in cognitive aging related to later-life exposure to ambient air pollution.
Sex difference in the association between ambient air pollution and cognitive aging remained unclear. This current study aimed to assess the impacts of long-term exposure to major air pollutants on cognitive performance among Chinese middle-aged and older adults, and explore whether these associations could be modified by sex. By deriving longitudinal data from four waves of the China Health and Retirement Longitudinal Study, we included 13,507 participants aged 45+ years who had at least two cognitive tests recorded from 2011 to 2018. We used a standardized questionnaire consisting of five domain-specific functions to measure global cognitive score. Based on well-validated spatiotemporal datasets, annual average concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were assigned to each enrollee at prefectural city level and at the simulated residential addresses through Monte Carlo simulation approach. Linear mixed-effects models were applied to assess the impacts of major air pollutants on cognitive function with multiple adjustments. Sex-stratified analyses were performed to examine the potential effect modification on these associations. To enhance the interpretability of our results, we also compared the estimated effects of air pollutants with the effect of aging on cognitive function. We evaluated 38,950 records of cognitive function tests, of which 44.0% were from women. An increase of 10-μg/m3 in PM2.5, NO2 and O3 exposure were associated with 0.36 (95% confidence interval: -0.40, -0.31), 0.51 (-0.60, -0.43) and 0.26 (-0.47, -0.06) points decline in global cognitive score, respectively, equivalent to the effect of aging by 2.8-5.0 years. Sex-stratified analyses suggested significantly greater cognitive impairment associated with air pollutants in women than men. We found reversely J-shaped concentration-response relationships between ambient air pollutants and cognitive decline in both sexes. Main findings on sex-specific associations were robust to the adjustments for covariates, inclusion criteria, and co-pollutant analyses, as well as sensitivity analyses based on simulation-based exposure for PM2.5 and NO2. Later-life exposure to ambient air pollution may accelerate cognitive aging of middle-aged and older adults, suggesting significant sex disparity with higher vulnerability in women.


Analysis of the impact of fatty acid metabolism on immunotherapy for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC), a malignancy with a very dismal prognosis, has drawn a lot of attention, particularly in East Asia, where morbidity and mortality are higher. Although new information about the role of fatty acids (FAs) in HCC is constantly being discovered, it is still vital to investigate how FA metabolism affects the prognosis, immune microenvironment, and responsiveness of HCC to immunotherapy as a whole. To determine the significance of FA metabolism in HCC immunotherapy, we first evaluated HCC samples from the single-cell dataset GSE151530. The TCGA-LIHC cohort and GSE140901 were further studied to identify the impact of FA metabolism on prognosis, immune microenvironment, drug sensitivity, and immunotherapy response by developing a fatty acid prediction index (FPI). The heterogeneity and similarity of the involvement of FA metabolism in pan-cancer is also investigated. Combining single-cell and bulk analyses, we confirmed that FA metabolism regulates tumor malignancy, prognosis, immune microenvironment, drug sensitivity, and immunotherapy response in patients with HCC. Moreover, it can have a considerable impact on the physiological activities of hepatocellular cancer. In addition, we demonstrate that FA metabolism has a comparable or same role in many malignancies. Our investigation shows the crucial regulatory role of FA metabolism in HCC and suggests a potential therapeutic method for HCC patients, which may improve their survival.


Strange Vibes - Novel Presentation of Prostatitis.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has significant variability in its presentation. In this study, we present 2 novel cases of prostatitis in which "buzz" is described as the primary pain symptom. These cases describe patients with the primary complaint of "cell phone-like buzzing" within the perineum, with accompanying urinary symptoms consistent with prostatitis. CP/CPPS is a multifactorial disease within which psychological, inflammatory, neurologic, and neuromuscular etiologies are at play. As in other disease descriptions, a buzzing sensation represents the interaction of multiple pathways that have significant overlay with CP/CPPS. As such, we believe buzzing might represent a new symptom of CP/CPPS.


Maxillary superimposition: a comparison of three methods for cephalometric evaluation of growth and treatment change.
Two anatomic methods are statistically compared with the implant method for superimposing serial head films in 18 subjects with metallic implants. Findings showed that the "best fit" method--that is, superimposition along the palatal plane registered at ANS--traditionally used by orthodontists, significantly underestimates the eruption of the teeth by 30% to 50%. The "structural method," which is based on the use of stable structures in the maxilla, showed no significant differences in vertical displacement of selected landmarks in comparison with the implant method.


"I Just Wanted Support": Examining How LDS Clergy May Effectively Minister to Sexual and Gender Minority Congregants.
This study explored why members of the Church of Jesus Christ of Latter-day Saints (LDS) who identify as sexual or gender minorities (SGM) speak with clergy regarding their SGM identities, as well as what LDS SGMs find helpful and unhelpful in these conversations. A sample of 25 current or former LDS SGMs participated in semi-structured interviews, which were analyzed using thematic analysis. Participants reported six overarching reasons for talking with clergy, including church procedures, seeking guidance, seeking emotional comfort, seeking repentance, seeking openness, and other people's initiation. Participants reported several ways clergy were helpful, including empathic listening, openness, and affirmative spiritual care. Participants further reported several ways clergy were unhelpful, including punishing, lacking empathic listening, having a limited worldview, and pathologizing. Clergy may benefit from understanding why LDS SGMs are speaking with them, and from utilizing helpful approaches such as empathic listening skills in their ministering efforts.


Transcriptomics and the mechanisms of antidepressant efficacy.
The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response. Blood samples were taken from a subset of depressed patients from the GENDEP study (n=136) before and after eight weeks of treatment with either escitalopram or nortriptyline. Transcriptomic data were obtained from these samples using Illumina HumanHT-12 v4 Expression BeadChip microarrays. When analysing individual genes, we observed that changes in the expression of two genes (MMP28 and KXD1) were associated with better response to nortriptyline. Considering connectivity between genes, we identified modules of genes that were highly coexpressed. In the whole sample, changes in one of the ten identified coexpression modules showed significant correlation with treatment response (cor=0.27, p=0.0029). Using transcriptomic approaches, we have identified gene expression correlates of the therapeutic effects of antidepressants, highlighting possible molecular pathways involved in efficacious antidepressant treatment.


Organoids and Their Research Progress in Plastic and Reconstructive Surgery.
Organoids are 3D structures generated from stem cells. Their functions and physiological characteristics are similar to those of normal organs. They are used in disease mechanism research, new drug development, organ transplantation and other fields. In recent years, the application of 3D materials in plastic surgery for repairing injuries, filling, tissue reconstruction and regeneration has also been investigated. The PubMed/MEDLINE database was queried to search for animal and human studies published through July of 2022 with search terms related to Organoids, Plastic Surgery, Pluripotent Stem Cells, Bioscaffold, Skin Reconstruction, Bone and Cartilage Regeneration. This review presents stem cells, scaffold materials and methods for the construction of organoids for plastic surgery, and it summarizes their research progress in plastic surgery in recent years.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The role of free radicals in the pathogenesis of amiodarone toxicity.
In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity. Rats were treated with amiodarone alone (500 mg/kg body weight per day) or together with antioxidants (silibinin or MTDQ-DA: 50 mg/kg body weight per day) or with either antioxidant alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days pretreatment). In vitro, amiodarone induced a dose-dependent chemiluminescence signal, which was inhibited by the two dihydroquinolin-type antioxidants (MTDQ-DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that simultaneous treatment with silibinin partially prevented the liver homogenate superoxide anion radical scavenger capacity decreasing effect of amiodarone. Amiodarone treatment caused a significant increase of NADPH and Fe3+ induced lipid peroxidation in the liver microsomal fraction, which antioxidants (silibinin, MTDQ-DA) were unable to prevent. Light microscopy of the lung tissue in amiodarone-treated rats showed accumulation of foamy macrophages with thickening of the interalveolar septa, pneumonitis, and variable interstitial fibrosis. Antioxidant treatment did not prevent these changes. Electron micrographs of lung from amiodarone-treated rats showed lysosomal phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome number and size. In contrast to rats treated with amiodarone alone, those treated with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01); the lysosome size, shape, and internal characteristics remained the same. Simultaneous treatment with silibinin and amiodarone decreased lysosomal phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment with MTDQ-DA and amiodarone did not show any beneficial effect. Pulse radiolysis and cobalt 60-gamma (60Co-gamma) radiolysis studies showed that the main free radical product in a reducing environment was a very reactive aryl radical formed after the partial deiodination of the amiodarone molecule. The radiosensitizing effect of amiodarone was also verified in rat liver microsomal preparations using in vivo amiodarone with or without MTDQ-DA pretreatment and 60Co-gamma irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ-DA). In vivo, the MTDQ-DA treatment also had a radiosensitizing effect; however, the in vitro addition of both antioxidants resulted in a radioprotective effect. The aryl radical also may emerge in vivo during the metabolism of amiodarone. These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well-established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.


Racial Disparities in Low Birthweight Risk: an Examination of Stress Predictors.
This paper describes racial disparities in low birthweight (LBW) risk between Black women and White women and examines the relationship between race and stressors such as socioeconomic factors, access to health care, and social and health characteristics. We analyzed data from the National Survey of Family Growth dataset collected in the USA between 2006 and 2010 (N = 1516). Multivariate logistic regression models were performed. Prevalence of LBW was 5.6 % for pregnancies among White women and 12.2 % among Black women. Black women who had a LBW baby had a lower socioeconomic status (e.g., received assistance to pay for delivery of the baby and public assistance in the prior year). Black women who had a LBW baby were more likely to have reported having good health compared with White women (67.8 vs. 45.1 %, p < .10). Pregnancies of Black women were 2.6 times more likely (odds ratio (OR) = 2.33; 95 % confidence interval (CI), 1.12-6.04) to result in a LBW baby than pregnancies among White women. Pregnancies of women in the income group of 300 % or higher than the poverty level were less likely to be associated with a LBW baby than those among women in the 150-299 % income group (p < .10). Obese women were less likely to have LBW children than those who were underweight or normal weight (p < .10). Among pregnancies of White mothers (n = 943), the only significant variable was self-reported health status. White women who reported having poorer health were 3.7 times more likely to have LBW than those who reported having better health (p < .10). Among Black mothers, the only predictor that was negatively associated with an increased likelihood of having a LBW baby was the SES stressor related to receiving public assistance. Racial differences between Black and White women were observed in LBW risk based on socioeconomic factors. We analyzed a large number of stressors, but racial differences remained even after taking these stressors into account. Future policies and research should continually address these differences to decrease LBW risk within and across racial groups.


Visiting and observing: reflections on clinical observer visits to Neuropsychiatry, Royal Melbourne Hospital.
To describe and provide experiential reflections on a model of continuing professional development in psychiatry for development and maintenance of specialised skills. For clinical psychiatrists working in smaller population centres, clinical observer visits with peers may be a useful method to develop, improve and calibrate knowledge and skills. Such potential benefits may be even more marked for specialised fields of psychiatry, such as neuropsychiatry.


A comparison of receptive and non-receptive plasma membrane areas of photoreceptor cells in the leech, Hirudo medicinalis.
Microvillar (receptive) and external (non-receptive) portions of the plasmalemma of photoreceptor cells of Hirudo were compared electron microscopically in thin sections and freeze-fracture replicas. A morphometric approximation showed that the surface area of the microvillar membrane is about 19 times larger than that of the external membrane. The microvillar membrane most probably undergoes extensive membrane turnover. In both segments of the membrane the particles associated with the P- and the E-fracture faces are randomly distributed except at some specific sites. The particles adhere predominantly to the P-faces. The particle densities on the fracture faces of the microvillar membrane differ from those of the external membrane. The P-face particles of the external membrane appear to be larger than those of the microvillar membrane. It is suggested that the P-face particles of the microvillar membrane represent sites where the photopigment is incorporated into the membrane. The distinguishing structural features correspond to the functional differences postulated for both portions of the plasma membrane.


Genetic evaluation and characterization of behavioral resistance to imidacloprid in the house fly.
Insecticide resistance in pest populations is an increasing problem in both urban and rural settings due to over-application of insecticides and lack of rotation among insecticidal chemical classes. The house fly (Musca domestica L.) is a cosmopolitan pest fly species implicated in the transmission of numerous pathogens. The evolution of insecticide resistance long has been documented in house flies, with resistance reported to all major insecticide classes. House fly resistance to imidacloprid, the most widely used neonicotinoid insecticide available for fly control, has evolved in field populations through both physiological and behavioral mechanisms. Previous studies have characterized and mapped the genetic changes that confer physiological resistance to imidacloprid, but no study have examined the genetics involved in behavioral resistance to imidacloprid to date. In the current study, several approaches were utilized to characterize the genetics and inheritance of behavioral resistance to imidacloprid in the house fly. These include behavioral observation analyses, preference assays, and the use of genetic techniques for the identification of house fly chromosome(s) carrying factors. Behavioral resistance was mapped to autosomes 1 and 4. Inheritance of resistance was shown to be neither fully dominant nor recessive. Factors on autosomes 1 and 4 independently conferred contact-dependent avoidance of imidacloprid and a feeding preference for sugar alone or for sugar with dinotefuran, another neonicotinoid insecticide, over imidacloprid. This study serves as the first linkage analysis of a behavioral trait in the house fly, and provides new avenues for research regarding inherited behavior in the house fly and other animals.


Lp-PLA2: inflammatory biomarker of vascular risk in multiple sclerosis.
A member of the A2 phospholipase superfamily, the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2), is involved in atherogenic processes. Lp-PLA2 mass and activity were measured by the enzyme-linked immunosorbent assay and by a colorimetric method, respectively, and compared among 63 multiple sclerosis (MS) patients and 47 age-matched healthy controls (HCs). Lp-PLA2 plasma levels were significantly higher in MS patients (236.7 ± 10 ng/ml) compared to HCs (197.0 ± 7 ng/ml) (p = 0.003), but LP-PLA2 activity did not differ between the two groups. Both Lp-PLA2 plasma mass and activity were higher in secondary progressive (mass 247.0 ±15.5 ng/ml, p = 0.05; activity 156.1 ±6 nmol/min/ml, p = 0.003) compared to relapsing-remitting MS patients (mass 227.0 ± 16 ng/ml; activity 128.8 ± 5 nmol/min/ml) and compared to HCs. Lp-PLA2 plasma activity was associated with measures of MS clinical disability. However, this association was attenuated after adjustment for the components of lipid profiles.


Non-functioning pituitary macroadenomas: Benefit from early growth hormone substitution after surgery.
Data suggests that substitution of GH in GH-deficient patients may improve quality-of-life and reduce insufficiency-associated-symptoms. Unlike in corticotroph, thyreotroph, or gonadotroph-insufficiency, GH-substitution is usually not started within the first 6-12months after surgery. We aimed to investigate the effect of early-GH-substitution on body-composition, metabolic and pituitary-laboratory-tests, and quality-of-life. Data was reviewed from 21 adult-patients who were diagnosed with insufficiency of GH-axis using insulin-hypoglycemia-test. We retrospectively assessed body-composition, metabolic and pituitary-laboratory-tests and quality-of-life for a period of 52-weeks after pituitary-surgery in patients with early GH-substitution (= treated-group, 11-patients) and no GH-substitution (= untreated group, 10-patients). Follow-up-IGF-I-levels of the treated-group stayed within the normal range and differed significantly from the untreated-group. Bioelectrical-impedance-analysis showed a significant decrease of impedance, a significant increase of lean-body-mass and a significant difference in health status in the treated group (p<0.05). Average increase in HDL-level was 2.1mg/dl in the untreated compared to an average decrease of 0.2mg/dl in the treated-group. Lp(a)-levels were reduced by 4.1mg/dl in the treated and by 2.7mg/dl in the untreated-group. Both groups showed an initial-mean-life-satisfaction below average (-0.9 and -1.2). Within one year after surgery mean-health-status improved in both groups. The difference in health-status after 1-year compared to the health-status of the previous year was statistically different between both groups with a greater benefit in the treated-group. Finally there was a trend detectably pointing towards an improvement in pituitary-function (LH- and FSH-recovery) if GH was substituted. Early GH-substitution leads to a significant improvement in quality-of-life and body-composition after pituitary-surgery. It is possible that pituitary-function recovers more with early-GH-substitution.


Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity.
Membrane-associated guanylate kinase homologs (MAGUKs) may play a role in cellular functions preventing tumorigenesis as indicated by the neoplastic phenotype caused by genetic loss of the MAGUK Dlg in Drosophila. To test this possibility, we examined the expression and subcellular localization of the tight junction MAGUK ZO-1, as well as the cell adhesion molecule E-cadherin, in paraffin-embedded breast cancer samples, using immunohistochemistry and confocal microscopy. As expected, normal tissue showed intense staining for ZO-1 at the position of the epithelial tight junctions, but this staining was reduced or lost in 69% of breast cancers analyzed (n = 48). In infiltrating ductal carcinomas (n = 38) there was a reduction in staining in 42% of well differentiated, in 83% of moderately differentiated and 93% of poorly differentiated tumors. ZO-1 staining was positively correlated with tumor differentiation (P = .011) and more specifically with the glandular differentiation of tumors (P = .0019). Reduction in ZO-1 staining was strongly correlated with reduced E-cadherin staining (P = 4.9 x 10(-5)). The results suggest that down-regulation of ZO-1 expression and its failure to accumulate at cell junctions may be causally related to cancer progression. To detect loss of heterozygosity, the ZO-1 gene tjp-1 was mapped relative to other markers in 15q13 and polymorphic markers flanking tjp-1 were identified. The marker D15S1019 showed loss of heterozygosity in 23% of informative tumors (n = 13). Loss of a tjp-1-linked marker suggests that genetic loss may, in some cases, be responsible for the reduction in ZO-1 expression in breast cancer.


Reader variability in breast density estimation from full-field digital mammograms: the effect of image postprocessing on relative and absolute measures.
Mammographic breast density, a strong risk factor for breast cancer, may be measured as either a relative percentage of dense (ie, radiopaque) breast tissue or as an absolute area from either raw (ie, "for processing") or vendor postprocessed (ie, "for presentation") digital mammograms. Given the increasing interest in the incorporation of mammographic density in breast cancer risk assessment, the purpose of this study is to determine the inherent reader variability in breast density assessment from raw and vendor-processed digital mammograms, because inconsistent estimates could to lead to misclassification of an individual woman's risk for breast cancer. Bilateral, mediolateral-oblique view, raw, and processed digital mammograms of 81 women were retrospectively collected for this study (N = 324 images). Mammographic percent density and absolute dense tissue area estimates for each image were obtained from two radiologists using a validated, interactive software tool. The variability of interreader agreement was not found to be affected by the image presentation style (ie, raw or processed, F-test: P > .5). Interreader estimates of relative and absolute breast density are strongly correlated (Pearson r > 0.84, P < .001) but systematically different (t-test, P < .001) between the two readers. Our results show that mammographic density may be assessed with equal reliability from either raw or vendor postprocessed images. Furthermore, our results suggest that the primary source of density variability comes from the subjectivity of the individual reader in assessing the absolute amount of dense tissue present in the breast, indicating the need to use standardized tools to mitigate this effect.


[Interactive Health Literacy, Sociodemographic Characteristics and the Uptake of Psychotherapeutic or Pharmacological Interventions - are there Social Inequalities in the Treatment of Social Anxiety Disorder?]
The aim is to investigate the association between sociodemographic characteristics and the interactive health literacy and the time to treatment of social anxiety disorder. An online survey of N = 311 patients was carried out (response rate 54.1 %). Descriptive statistical analysis and a logistic regression analysis were carried out. The respondents are on average 46 years old (20-81), 59 % are women. Older age (OR 2,579), not living in partnership (OR 1,963), fear of personal contact (OR 5,716) and low (OR 3,585) or moderate (OR 3,144) interactive health literacy were significantly associated with the time to treatment. The data suggest that social inequalities exist regarding the use of psychotherapeutic or pharmacological interventions in people with social anxiety disorder.


Uncertainty associated to the analysis of organochlorine pesticides in water by solid-phase microextraction/gas chromatography-electron capture detection--evaluation using two different approaches.
As the performances of analytical instrumentation are being gradually enhanced, the limits of detection become increasingly lower, allowing more environmental contaminants to be determined in different matrices. Problems emerge when dealing with data from different origins, once the uncertainty of the results is difficult to be compared, especially if its calculation procedure is rather different, as very often happens. Samples of two organochlorine pesticides of somewhat opposite characteristics (lindane and heptachlor, classified as persistent organic pollutants--POPs) were analyzed in aqueous media using headspace solid-phase microextraction (SPME) prior to gas chromatography-electron capture detection (GC-ECD) and this methodology was in-house validated. Detection limits of 0.097 and 0.050 microg l(-1), average intermediate precision of 11.6% and 27.5%, and average recovery of 95.6% and 103.0%, for lindane and heptachlor, respectively, were found. In the absence of available interlaboratory studies to assess the reliability of the results, the expanded uncertainty was calculated following two different approaches (bottom-up/Eurachem and modified top-down) and the results were compared. Globally it was clearly shown that, for both pesticides, the lower the concentration range, the higher the uncertainty associated to the results. Expanded uncertainties estimated by bottom-up/Eurachem approach varied from 51% to 14% for a lindane concentration range of 0.1-1 microg l(-1), and from 48% to 24% for a heptachlor range of 0.1-2 microg l(-1). Modified top-down approach pointed to 44% (lindane and heptachlor) in the same ranges, meaning that a uniform procedure for uncertainty estimation should be adopted.


Pharmacokinetics of ethylene in man by on-line laser photoacoustic detection.
The pharmacokinetics of ethylene are determined using laser-based photoacoustic detection and a closed chamber setup. Concentration-time data are analyzed using a two-compartment and a physiologically based pharmacokinetic (PBPK) model. Endogenous production was 92 +/- 13 pmol/h/kg for the two-compartment model and 75 +/- 10 pmol/h/kg for the PBPK model. These values agree with previous work at our department but are significantly lower than published values based on gas chromatography. The blood:air partition coefficient in the PBPK model was determined by curve fitting, because simulations based on published values did not agree well with data. Curve fitting gave a value of 0.092 +/- 0.029. The real-time nature and high sensitivity of photoacoustic detection make it a useful addition to gas chromatography in closed chamber studies.


The Significance of PET/CT in the Initial Staging of Hodgkin Lymphoma: Experience Outside Clinical Trials.
To examine the real-life impact of baseline positron-emission tomography/computed tomography (PET/CT) in Hodgkin lymphoma (HL). A total of 162 consecutive patients with HL were retrospectively studied. Disease was up-staged in 26 patients (16%) and down-staged in 9 (6%). However, treatment strategy was modified in only 10 patients (6% of total). Involved field radiotherapy was delineated according to PET/CT in 36/66 patients (59%). These treatment modifications did not significantly affect outcome. Moreover, three potent prognostic parameters were identified: the number of involved sites, maximum standardized uptake value (SUVmax), and the product of SUVmax and maximal largest lesion diameter, as a surrogate of total lesion glycolysis. All three significantly correlated with 5-year freedom from disease progression p=0.004, p=0.009 and p=0.04, respectively). Baseline PET/CT findings may lead to treatment modification in <15% of patients with HL without a significant impact on outcome. Certain PET/CT parameters have potent prognostic significance.


Breastfeeding is Possible: A Systematic Review on the Feasibility and Challenges of Breastfeeding Among Breast Cancer Survivors of Reproductive Age.
Breastfeeding is the biologically normative mode of feeding human infants, and reduces the risk of breast cancer for mothers. This systematic review assesses engagement in breastfeeding and the factors associated with breastfeeding among breast cancer survivors. An online literature search was performed using the PubMed, Embase, CINAHL, PsychInfo, and Web of Science databases. Inclusion criteria were original research articles written in English, published in peer-reviewed journals from 1 January 1990 to 25 November 2019, and included data on breast cancer survivors who attempted breastfeeding. Thirteen studies were included in the systematic review. Between 7.7 and 90.9% of women attempted breastfeeding. Breastfeeding among participants varied from a few weeks to approximately 2 years. Common factors leading to breastfeeding were use of the contralateral breast, support from others, lactation counseling and advice from an International Board-Certified Lactation Consultant, being motivated to breastfeed, frequent feedings, and use of galactagogues. Common barriers were medical counseling against breastfeeding, insufficient milk production, lack of support, refusal of the infant to breastfeed from the treated breast, and being tired from relying on one breast. Breastfeeding from the unaffected breast is feasible for some breast cancer survivors. Successful breastfeeding may require multilevel support and expert advice.


Mendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease.
Coronary artery disease (CAD) is a leading cause of death in patients with systemic lupus erythematosus (SLE). Despite clinical evidence supporting an association between SLE and CAD, pleiotropy-adjusted genetic association studies are limited and focus on only a few common risk loci. Here, we identify a net positive causal estimate of SLE-associated non-HLA SNPs on CAD by traditional Mendelian randomization (MR) approaches. Pathway analysis using SNP-to-gene mapping followed by unsupervised clustering based on protein-protein interactions (PPIs) identifies biological networks composed of positive and negative causal sets of genes. In addition, we confirm the casual effects of specific SNP-to-gene modules on CAD using only SNP mapping to each PPI-defined functional gene set as instrumental variables. This PPI-based MR approach elucidates various molecular pathways with causal implications between SLE and CAD and identifies biological pathways likely causative of both pathologies, revealing known and novel therapeutic interventions for managing CAD in SLE.


Nitrogenase--hydrogenase interrelationships in Rhizobia.
A review is given of the properties of the hydrogenase present in Rhizobium bacteriods together with a discussion and evidence of the function of the enzyme in relationship to nitrogen fixation. The efficiency with which nodules fix nitrogen i.e. the amount of hydrogen evolved as a ratio of the total electron flow through nitrogenase, is considered and the recycling of hydrogen is discussed. Attention is drawn to recent work, in which plants which have nodules containing hydrogenase have been shown to fix more nitrogen and increase more in dry matter than plants with nodules without hydrogenase.


Understanding Social Situations (USS): A proof-of-concept social-cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis.
In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social-cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record


Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with micro electrode array.
Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks.


Plasma neurofilament light-chain and phosphorylated tau as biomarkers of disease severity in Huntington's disease: Korean cohort data.
To investigate neurofilament light chain (NfL), phosphorylated tau (p-Tau) and total tau (t-Tau) as plasma markers for clinical severity in Korean Huntington's disease (HD) cohort. Genetically-confirmed 67 HD patients participated from 13 referral hospitals in South Korea. The subjects were evaluated with the Unified Huntington's Disease Rating Scale (UHDRS), total motor score (TMS) and total functional capacity (TFC), Mini-Mental Status Examination (K-MMSE), Montreal Cognitive Assessment (MoCA-K), and Beck's depression inventory (K-BDI). We measured plasma NfL, p-Tau and t-Tau concentrations using single-molecule array (SIMOA) assays. Stages of HD were classified based on UHDRS-TFC score and plasma markers were analyzed for correlation with clinical severity scales. Plasma NfL was elevated in both 6 premanifest and 61 full manifest HD patients compared to the reference value, which increased further from premanifest to manifest HD groups. The NfL level was not significantly correlated with UHDRS TMS or TFC scores in manifest HD patients. Plasma p-Tau was also elevated in HD patients (p = 0.038). The level was the highest in stage III-V HD (n = 30) group (post-hoc p < 0.05). The p-Tau was correlated with UHDRS TFC scores (adjusted p = 0.002). Plasma t-Tau neither differed among the groups nor associated with any clinical variables. This study supports plasma NfL being a biomarker for initial HD manifestation in Korean cohort, and a novel suggestion of plasma p-Tau as a potential biomarker reflecting the clinical severity in full-manifest HD.


Pediatric renal malignancy diagnosis is associated with significant burden of care for families.
New childhood cancer diagnoses require timely, complex care coordination and cause considerable logistic burden for families. We used renal tumors as a model to examine healthcare utilization and cost following new solid tumor diagnosis. Children (ages 0-21) with International Classification of Disease (ICD) codes for renal malignancy and subsequent nephrectomy were identified from North Carolina Medicaid claims data (2014-2020). We stratified patients by duration of follow-up, then quantified healthcare utilization and billing totals. Eighty-one children met study criteria. Median age at diagnosis was 3 years (interquartile range [IQR]: 1-5). Median family monthly earned income was $0. One month following diagnosis, children cumulatively spent a median of 16 days receiving medical care (IQR: 10-20), 28 days at 3 months (IQR: 21-43), and 50.5 days at 1 year (IQR: 35-94.5). Children cumulatively spent a median 12 days as inpatients during the first 3 months (IQR: 7-17) and 13.5 days at 1 year (IQR: 8.5-37). Children cumulatively completed a median 12 outpatient encounters at 3 months (IQR: 7-17) and 26 at 1 year (IQR: 12-36). At 1 year, median Medicaid claim reimbursements for children with renal malignancy was $50,041 (IQR: $36,670-$80,734). In examining healthcare utilization in children with renal tumor diagnoses, the substantial number of days spent in medical facilities greatly impacts the burden of care on families, especially for those with limited financial resources. Awareness of this logistic strain on families and careful planning to consolidate patient visits may improve the navigability of pediatric cancer regimens for families, particularly those with limited resources.


Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats.
Epalrestat, an aldose reductase inhibitor (ARI), was adopted to improve the function of peripheral nerves in diabetic patients. The aim of this study was to investigate whether epalrestat could restore the erectile function of diabetic erectile dysfunction using a rat model. From June 2016, 24 rats were given streptozocin (STZ) to induce the diabetic rat model, and epalrestat was administered to ten diabetic erectile dysfunction (DED) rats. Intracavernous pressure (ICP) and mean systemic arterial pressure (MAP), levels of aldose reductase (AR), nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS), α-smooth muscle antigen (α-SMA), and von Willebrand factor (vWF) in the corpus cavernosum were analyzed. We discovered that epalrestat acted on cavernous tissue and partly restored erectile function. NGF and nNOS levels in the corpora were increased after treatment with epalrestat. We also found that the content of α-SMA-positive smooth muscle cells and vWF-positive endothelial cells in the corpora cavernosum were declined. Accordingly, epalrestat might improve erectile function by increasing the upregulation of NGF and nNOS to restore the function of the dorsal nerve of the penis.


Preliminary study on the carcinogenic activity of the fungicide manganese ethylenebisdithiocarbamate in the adult newt. Triturus cristatus carnifex.
Percutaneous exposure of adult newts to the fungicide manganese ethylenebisdithiocarbamate (maneb) at 3 concentration levels (0.5, 2.5 and 5.0 ppm) for a total of 19.23 weeks did not result in the induction of any neoplasms.


Quality and Patient Safety Teams in the Perioperative Setting.
Quality and patient safety teams in the perioperative setting can provide perioperative personnel with a safety net to prevent avoidable errors, which is a necessity in today's complex surgical world. The primary goal of the quality and patient safety team should be to develop and implement a perioperative quality and patient safety strategic plan. The mission of the plan can be developed by surveying facility employees, choosing a quality methodology, and using an evidence-based approach to develop and implement quality programs and processes. To create and sustain a quality and patient safety team, it is important to select a heterogeneous group; define team roles; identify day-to-day, weekly, and monthly team responsibilities; actively participate in facility committees, meetings, and new employee orientation; conduct audits; and schedule project time.


Humic acids as proxies for assessing different Mediterranean forest soils signatures using solid-state CPMAS 13C NMR spectroscopy.
Humic acids (HAs) of four representative forest soils profiles from Central Spain (two with different vegetation - pine and oak - but same parent material - granitie, and two with same vegetation - holm oak - but different parent material - granite and limestone) were investigated by solid-state cross polarization with magic angle spinning (13)C nuclear magnetic resonance (NMR) spectroscopy. The objectives included the investigation of the impact of different forest properties on HA composition, assessing how the structural characteristics of the HA vary with soil depth, and evaluating the role of HA as surrogates for mapping the different forest soils signatures using structural data derived from (13)C NMR spectroscopy. On average, alkyl C is the dominant C constituent (38-48% of the total NMR peak area) in all HA samples, followed by aromatic (12-22%) and O-alkyl C (12-19%), and finally carboxyl C (7.0-10%). The NMR data also indicated that HA composition is likely to be differently affected by the soil physico-chemical properties and type of forest vegetation. The structural characteristics of the HA from soil under oak did not differ broadly downward in the profile, whereas soil HA under pine forest exhibits a somewhat higher recalcitrant nature as a consequence of a higher degree of decomposition. The soil HA from holm oak forests differed from the other two forest soils, exhibiting a progressive decomposition of the alkyl C structures with increasing depth, while the carbohydrate-like indicator (O-alkyl C) is apparently being protected from mineralization in the horizons below the ground level. Overall, these differences in soil HA NMR signatures are an important diagnostic tool for understanding the role of different soil environmental factors on the structural composition of HA from Mediterranean forest soils.


Cold tolerance and freeze-induced glucose accumulation in three terrestrial slugs.
Cold tolerance and metabolic responses to freezing of three slug species common in Scandinavia (Arion ater, Arion rufus and Arion lusitanicus) are reported. Autumn collected slugs were cold acclimated in the laboratory and subjected to freezing conditions simulating likely winter temperatures in their habitat. Slugs spontaneously froze at about -4 °C when cooled under dry conditions, but freezing of body fluids was readily induced at -1 °C when in contact with external ice crystals. All three species survived freezing for 2 days at -1 °C, and some A. rufus and A. lusitanicus also survived freezing at -2 °C. (1)H NMR spectroscopy revealed that freezing of body fluids resulted in accumulation of lactate, succinate and glucose. Accumulation of lactate and succinate indicates that ATP production occurred via fermentative pathways, which is likely a result of oxygen depletion in frozen tissues. Glucose increased from about 6 to 22 μg/mg dry tissue upon freezing in A. rufus, but less so in A. ater and A. lusitanicus. Glucose may thus act as a cryoprotectant in these slugs, although the concentrations are not as high as reported for other freeze tolerant invertebrates.


Evaluation of intraocular lens position during phacoemulsification using intraoperative spectral-domain optical coherence tomography.
To assess the position of intraocular lenses (IOLs) at the end of standard phacoemulsification with intraoperative spectral-domain optical coherence tomography (SD-OCT). Department of Ophthalmology, Rudolf Foundation Hospital, Vienna, Austria. Prospective case series. Standard phacoemulsification with IOL implantation was performed. The Rescan 700 SD-OCT system was used for intraoperative imaging. The anterior segment of the eye was scanned using SD-OCT at the end of the surgery. The distance from the IOL optic center and the IOL optic edge to the posterior capsule was measured postoperatively using graphic software. The study comprised 74 patients (101 eyes). The mean axial length was 23.97 mm (range 21.43 to 28.61 mm). The mean IOL power was 20.39 diopters (D) (range 6.5 to 27.5 D). Contact between the IOL and posterior capsule was absent in 88 cases (87.13%), and partial or full contact was present in 13 cases (12.87%). The mean distance between the IOL central optic and posterior capsule was 0.71 pixel (range 0.06 to 1.38 pixels) in 99 cases (98.02%). In 42 cases (57.53%), partial contact between the IOL edges and the posterior capsule was noticed. The mean distance between the IOL edge and posterior capsule was 0.21 pixel (range 0.04 to 0.92 pixel). Intraoperative SD-OCT facilitated the imaging of IOL position during standard phacoemulsification. Contact between the IOL central optic and posterior capsule at the end of the surgery occurred rarely. Improved IOL design should be considered. Drs. Binder and Glittenberg are consultants to Carl Zeiss Meditech AG. None of the other authors has a financial or proprietary interest in any material or method mentioned.


Cardiovascular autonomic neuropathy in type 1 diabetic patients with and without peripheral neuropathy.
One hundred Type 1 diabetic patients (54 men, 46 women) mean age 28.9+/-8.4 years, were selected from among individuals referred to our hospital, with no previous diagnosis of diabetic chronic complications including diabetic neuropathy. After clinical and physical examinations, subjects were divided into two groups: with (n = 37) and without (n = 63) peripheral neuropathy. The percentage of subjects with cardiovascular autonomic neuropathy (AN), diagnosed by positive results to at least two of the five cardiovascular tests (Valsalva ratio, EI ratio, 30/15 ratio, blood-pressure response to standing up and handgrip test), was 40%: 72.9% in the group with peripheral neuropathy and 20.6% in the group without peripheral neuropathy (P < 0.0001). The prevalence of cardiovascular AN was related to the duration of the diabetes (P < 0.0001) and to HbA1c (P < 0.02). The presence of microalbuminuria and the existence of retinopathy were higher (P < 0.01 ) in group 1 (with peripheral neuropathy). Logistic regression analysis showed that only the presence of higher excretion of albumin is independently related to the presence of peripheral neuropathy. In conclusion, cardiovascular AN is frequent in Type 1 diabetes; furthermore, prevalence increases with the existence of peripheral neuropathy and with duration of the diabetes.


Baseline assessment of the hydrological network and land use in riparian buffers of Pampean streams of Uruguay.
The integrated assessment of stream networks and terrestrial land use contributes a critical foundation for understanding and mitigating potential impacts on stream ecology. Riparian zone delineation and management is a key component for regulating water quality, particularly in agricultural watersheds. We present a national assessment of riparian zone land uses according to stream order for the entire hydrological network in the Uruguayan landscape in Southeastern South America. We classified over 82,500 km of streams and rivers in Uruguay into seven Strahler order classes and delineated riparian buffers of 100 and 500 m, depending on stream order, covering a total of 13% of the terrestrial land area in Uruguay. Natural vegetation cover in riparian zones averaged 77% among basins, whereby natural grassland dominated first and second order stream buffers at 58% and 49%, respectively. This highlighted the importance of grasslands in headwater regions of the country. Riparian forests formed corridors along larger streams, representing a mere 9% of buffers in first order streams but reaching 46% of buffers of 6th order streams. Among the six major basins of Uruguay, we found differences in the relative importance of riparian forests and crop cover in headwater stream riparian zones, as well as differences in relative crop cover within riparian zones. Results show that streams in subtropical grassland landscapes originate in open grassland environments, which has major implications for thermal regimes, carbon inputs, and stream biodiversity. Riparian buffer management should consider geographic differences among different basins and ecoregions within Uruguay.


Modeling fetal cavum septum pellucidi width by quantile regression at 18-34 weeks of gestation: A prospective cross-sectional study.
Develop charts for cavum septum pellucidi (CSP) following a standardized methodology and using quantile regression. The secondary objective was to assess the influence of fetal gender on the generated reference curves. In a cross-sectional prospective study 453 low-risk singleton pregnancies were evaluated at a gestational age interval between 18 and 34 weeks. The width of CSP were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). Differences between sex were evaluated. The measurement of CSP significantly increased with gestation and HC. Linear models better described the changes of CSP with GA and HC. The fits of CSP width with GA and HC were not significantly different. Male fetuses showed significantly higher CSP width when compared to female fetuses (u = 2.973; p = 0.005). We generated prospective nomograms of fetal CSP development using quantile regression and following a strict standardized methodology. These new charts may be useful to better identify abnormal cases at higher risk of associated anomalies. Further our findings underline the potential effect of gender in developing fetal brain.


Stereocontrolled synthesis of 1,2- and 1,3-diamine building blocks from aziridine aldehyde dimers.
Vicinal aziridine-containing diamines have been obtained with high syn-stereoselectivity from readily available aziridine aldehyde dimers in the Petasis borono-Mannich reaction. Subsequent solvent- and/or nucleophile-dependent ring-opening of the aziridine ring yields functionalized 1,2- and 1,3-diamines with high regioselectivity. The ring opening is also influenced by the substitution at the C3 position of the aziridine. A mechanistic rationale for the highly syn-selective three-component reaction is proposed.


Loss of ions in cavity ionization chambers.
Ion losses due to initial recombination, volume recombination, and back diffusion were each determined by measurements and calculations for different size cylindrical ionization chambers and spherical ionization chambers. By measuring signal currents from these ionization chambers irradiated with (60)Co gamma rays, two groups of ion losses were obtained. (Group 1) Ion loss due to initial recombination and diffusion, which changes proportionally to the inverse of the voltage applied to the ionization chambers; (and group 2) ion loss due to volume recombination, which changes proportionally to the inverse of the square of the applied voltage. The diffusion loss was obtained separately by computing electric field distributions in the ionization chambers. It was found that diffusion loss is larger than initial recombination loss for the cylindrical ionization chambers and vise versa for the spherical ionization chambers.


Effect of Concomitant Cardiac Arrest on Outcomes in Patients With Acute Coronary Syndrome-Related Cardiogenic Shock.
Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n = 769, 49%), the CA group (n = 804, 51%) was younger (62 vs 69 years, p <0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p <0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p = 0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p <0.001) and mortality (52% vs 37%, p <0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p <0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p = 0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.


Distribution of xanthine dehydrogenase and oxidase activities in human and rabbit tissues.
The activity of xanthine dehydrogenase in human postmortem tissues is surprisingly high in brain and heart; activity was found in most tissue samples, whereas many samples contained little or no oxidase activity. We have confirmed the high level of oxidase activity in liver in which tissue conversion of dehydrogenase to oxidase appears complete. We have also confirmed the virtual absence of either activity in fresh human placenta. Fresh rabbit tissues similarly show considerable dehydrogenase activity in brain and heart. In view of the stability and generalised distribution of dehydrogenase activity, our results suggest that some modification of existing ideas on the physiological and pathological roles of the enzyme may be needed.


Hemodynamic and morphologic changes of peripheral hepatic vasculature in chronic liver disease: a preliminary study by contrast-enhanced coded phase-inversion harmonic sonography.
To investigate whether observing the morphology of the peripheral hepatic vasculature and the hemodynamics of microbubble arrival time in these vessels can provide useful information for the diagnosis of liver disease, Five normal volunteers and 16 patients were studied by contrast-enhanced coded phase-inversion harmonic sonography. Vessel images of the peripheral vessels were observed in real time after intravenous injection of Levovist. The time when the microbubbles appeared in the peripheral vessels was measured. Three patterns of morphologic change of the peripheral hepatic vasculature were seen, marked, slight, and no abnormal changes. The microbubble arrival times at the peripheral vessels were all shorter in patients with cirrhosis than chronic hepatitis or normal subjects. Marked, slight, and no abnormal morphologic changes of the peripheral hepatic vasculature in patients with liver cirrhosis were found in five, one and zero of the six patients, respectively. Those patients with chronic hepatitis, were found in one, six and three of the ten patients, respectively. There was a significant difference among the different groups (P < 0.001). Evaluating the hemodynamics and morphology by contrast-enhanced coded pulse-inversion harmonic sonography may offer useful information in the diagnosis of liver disease.


New concepts in the assessment of syncope.
Significant progress has been made in the past 3 decades in our understanding of the various causes of loss of consciousness thanks to the publication of several important studies and guidelines. In particular, the recent European Society of Cardiology guidelines provide a reference standard for optimal quality service delivery. This paper gives the reader brief guidance on how to manage a patient with syncope, with reference to the above guidelines. Despite the progress made, the management of patients with syncope remains largely unsatisfactory because of the presence of a significant gap between knowledge and its application. Two new concepts aimed at filling that gap are currently under evaluation: syncope facilities with specialist backup and interactive decision-making software. Preliminary data have shown that a standardized syncope assessment, especially when coupled with interactive decision-making software, decreases admission rate and unnecessary testing and improves diagnostic yield, thus reducing cost per diagnosis. The long-term effects of such a new health care model on the rate of diagnosis and survival await future studies.


Cerebral microbleeds in patients with ischemic cerebrovascular disease taking aspirin or clopidogrel.
Cerebral microbleeds (CMBs) may be markers of intracerebral bleeding risk in patients receiving antithrombotic drugs. This study aimed to analyze CMBs and white matter hyperintensities (WMHs) in patients taking aspirin or clopidogrel.This retrospective study included patients with ischemic cardiovascular disease administered 75 mg/day aspirin (n = 150) or clopidogrel (n = 150, matched for age and gender) for >1 year (Affiliated Hospital of Inner Mongolia Medical University, China, from July, 2010 to July, 2015). Patients underwent T2-weighted imaging, T1-weighted imaging, diffusion-weighted imaging (DWI) and enhanced T2*-weighted angiography (ESWAN) imaging (3.0-Tesla scanner). Baseline vascular risk factors for CMBs and macroscopic bleeding (MB) were evaluated using univariate and multivariate analyses.The aspirin and clopidogrel groups did not differ significantly in baseline characteristics or prevalences of CMBs or MB. The odds of MB were higher in patients with CMBs than in patients without CMBs in both the aspirin (odds ratio, 95% confidence interval: 4.09, 1.93-8.68; P < .001) and clopidogrel (6.42, 2.83-14.57; P < .001) groups. The odds of WMHs were also higher in patients with CMBs in both the aspirin (3.28, 1.60-6.71; P = .001) and clopidogrel (4.09, 1.91-8.75; P < .001) groups. Patients receiving treatment for >5 years showed elevated risk of CMBs in the aspirin (0.17; 0.09-0.36; P < .001) and clopidogrel (0.15, 0.07-0.33; P < .001) groups as well as higher odds of MB in the aspirin (0.34, 0.16-0.71; P = .004) and clopidogrel (0.37, 0.17-0.80; P = .010) groups.The WMHs and MB were associated with CMBs in patients taking aspirin or clopidogrel for >1 year, and long-term use increased the risks of CMB and bleeding.


Epicutaneous patch testing: current trends and controversial topics.
In the 20th century, epicutaneous patch testing has played an integral and central role in the assessment of allergic contact dermatitis and therefore in general dermatologic practice. After recent verification of the safety and accuracy of patch testing by the Food and Drug Administration, domestic distribution of testing materials has resumed for the first time in 5 years. Because of the importance of this procedure, it is timely to review current standards of epicutaneous patch testing with emphasis on proper use and interpretation, clinical applications, trends in allergic contact dermatitis, and selected controversial issues.


[Natural history of primary biliary cirrhosis].
Primary biliary cirrhosis is a chronic cholestatic disease that generally appears in middle-aged women. The clinical course is slow and progressive, finally leading to cirrhosis. This disease has three forms of presentation: silent, asymptomatic and symptomatic. The silent form is characterized by the presence of antimitochondrial antibodies as the only abnormality. The silent and asymptomatic forms are less aggressive and have a slower clinical course. During the course of the disease, some patients remain asymptomatic. No distinguishing features between asymptomatic patients and those who develop symptoms have been identified. Survival is better in asymptomatic than in symptomatic patients and is excellent in patients who remain asymptomatic. The introduction of treatment with ursodeoxycholic acid has greatly prolonged the natural course of the disease. In patients with good therapeutic response, survival is similar to that in the general population. The clinical and laboratory variables associated with poor prognosis are age, bilirubinemia, albuminemia, prothrombin time, ascites, hepatic encephalopathy and advanced histological stage. Likewise, the development of varices and of hepatocellular carcinoma carries a poor prognosis. Bilirubinemia is, however, the most important variable to establish prognosis. There are distinct mathematical prognostic models that sensitively predict the probability of survival and are useful to determine disease severity in specific patients.


Syringomatous adenoma of the nipple: a case report.
We present a case of a 33-year-old woman who underwent excisional breast biopsy due to a left nipple mass. Histological examination revealed the morphologic and immunohistochemical pattern of syringomatous adenoma of the nipple. This is a rare lesion of the breast that can clinically mimic breast carcinoma, but harbors a benign and only locally aggressive course. Awareness of both the clinician and the pathologist for the possibility of diagnosing this tumor in the nipple region is mandatory to avoid mastectomy and lymph node dissection.


Meningeal metastases: clinical aspects and diagnosis.
The authors review the clinical and diagnostic aspects involved in leptomeningeal disease due to solid tumours, leukaemias and lymphomas. The importance of the combination of clinical findings with cerebral spinal fluid (CSF) examination and imaging studies in making an early diagnosis is underlined. The raising prevalence of this complication of systemic cancer deserves specific attention on the part of neurologists involved in consultation liason with general medicine and oncology.


Biochar amendment reassembles microbial community in a long-term phosphorus fertilization paddy soil.
This study investigates the effect of biochar amendment on microbial community structure and soil nutrient status in paddy soil that has been fertilized for an extended period of time, shedding light on sustainable agricultural practices. A 90-day incubation period revealed that biochar amendment, as opposed to long-term fertilization, significantly influenced the physicochemical properties and microbial composition of the soil. The microcosm experiment conducted using six treatments analyzed soil samples from a long-term rice ecosystem. We employed microbial biomarkers (phospholipid fatty acids, PLFAs; isoprenoid and branched glycerol dialkyl glycerol tetraethers, iGDGTs and brGDGTs; DNA) to assess microbial biomass and community structure. Biochar addition led to a decrease in PLFA biomass (15-32%) and archaeal iGDGT abundance (14-43%), while enhancing bacterial brGDGT abundance by 15-77%. Intact biochar increased archaeal and bacterial diversity, though fungal diversity remained unchanged. However, acid-washed biochar did not result in a uniform microbial diversity response. The abundance of various microbial taxa was changed by biochar amendment, including Crenarchaeota, Proteobacteria, Nitrospira, Basidiomycota, Halobacterota, Chloroflexi, Planctomycetota, and Ascomycota. Soil NH4+-N was found as the primary environmental factor impacting the composition of archaea, bacteria, and fungus in this study. These findings imply that the addition of biochar has a quick influence on the structure and activity of microbial communities, with fungi possibly having a critical role in acid paddy soil. This study contributes valuable knowledge for developing sustainable agricultural practices that promote healthy soil ecosystems. KEY POINTS: • Biochar type and phosphorus fertilization demonstrated an interactive effect on the diversity of archaea, but no such effect was observed for bacteria and fungi. • Soil fungi contribute to approximately 20% of the total phospholipid fatty acid (PLFA) content. • Biochar, especially acid-washed rice straw biochar, increases glucose metabolism in bacteria and archaea and decreases saprophytic fungi.


Identification of chromosomal breakpoints of cancer-specific translocations by rolling circle amplification and long-distance inverse PCR.
We describe the use of rolling circle amplification and long-distance inverse polymerase chain reaction (LD-PCR) to identify chromosomal breakpoints and fusion genes in cancer cells carrying acquired translocations. This approach produced enough template for 100 inverse PCR reaction from as little as 20 ng of patient DNA, consequently enabling the use of up to 500 times less patient DNA compared to standard inverse PCR. The method is based on identifying restriction sites in a putative breakpoint area in a cancer-specific translocation, followed by circularization and amplification of the restriction DNA products by using T4 DNA ligase and Phi29 enzyme, respectively. The amplified DNA thus obtained is used as a template in long-distance inverse PCR to amplify and detect the precise breakpoint of the chromosomal rearrangements in question by sequencing of the obtained PCR products. We demonstrate the feasibility of this approach by identifying fusion genes TAF15-ZNF384 (brought about by a (12;17)(p13;q21) translocation) and BCR-ABL1 (produced by a (9:22)(q34;q11.2) translocation) in five leukemia samples. The application of rolling circle amplification before inverse PCR may be particularly useful in the search for chromosomal breakpoints and fusion genes brought about by new translocations when only minute amounts of DNA are available from the sampled malignant lesion.


Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of Goalpha.
We examined the hypothesis that decreased inhibitory G protein function in diabetic neuropathy is associated with increased protein kinase C (PKC)-dependent phosphorylation of the Goalpha subunit. Streptozotocin-induced diabetic rats were studied between 4 and 8 weeks after onset of diabetes and compared with aged-matched healthy animals as controls. Opioid-mediated inhibition of forskolin-stimulated cyclic AMP was significantly less in dorsal root ganglia (DRGs) from diabetic rats compared with controls. Activation of PKC in DRGs from control rats was associated with a significant decrease in opioid-mediated inhibition of forskolin-stimulated cyclic AMP that was similar to the decrease in inhibition observed in DRGs from diabetic rats. Both basal and PKC-mediated labeling of Goalpha with 32Pi was significantly less in DRGs from diabetic rats, supporting increased endogenous PKC-dependent phosphorylation of Goalpha. Probing of immunoprecipitated Goalpha with an anti-phospho-serine/threonine specific antibody revealed a significant increase in baseline phosphorylation in diabetic DRGs. Activation of PKC produced a significant increase in phosphorylation in control DRGs but no significant increase in Goalpha in diabetic DRGs. Phosphorylation of PKC-alpha was increased, PKC-betaII was unchanged and PKC-delta decreased in diabetic DRGs. These results suggest that diminished inhibitory G protein function observed in DRGs neurons from diabetic rats involves an isoform-specific PKC-dependent pathway.


Sleep Characteristics According to Gender and Age Measured by Wrist Actigraphy.
The sleep/wake rhythm is one of the most important biological rhythms. Quality and duration of sleep change during lifetime. The aim of our study was to determine differences in sleep efficiency, movement, and fragmentation during sleep period between genders and according to age. Sleep period was monitored by wrist actigraphy under home-based conditions. Seventy-four healthy participants-47 women and 27 men participated in the study. The participants were divided by age into groups younger than 40 years and 40 years and older. Women showed lower sleep fragmentation and mobility during sleep compared to men. Younger women showed a higher actual sleep and sleep efficiency compared to older women and younger men. Younger men compared to older men had a significantly lower actual sleep, lower sleep efficiency and significantly more sleep and wake bouts. Our results confirmed differences in sleep parameters between genders and according to age. The best sleep quality was detected in young women, but gender differences were not apparent in elderly participants, suggesting the impact of sex hormones on sleep.