External Quality Assessment (EQA) for Molecular Diagnostics of Zika Virus: Experiences from an International EQA Programme, 2016⁻2018.
Quality Control for Molecular Diagnostics (QCMD), an international provider for External Quality Assessment (EQA) programmes, has introduced a programme for molecular diagnostics of Zika virus (ZIKV) in 2016, which has been continuously offered to interested laboratories since that time. The EQA schemes provided from 2016 to 2018 revealed that 86.7% (92/106), 82.4% (89/108), and 88.2% (90/102) of the participating laboratories reported correct results for all samples, respectively in 2016, 2017, and 2018. The review of results indicated a need for improvement concerning analytical sensitivity and specificity of the test methods. Comparison with the outcomes of other EQA initiatives briefly summarized here show that continuous quality assurance is important to improve laboratory performance and to increase preparedness with reliable diagnostic assays for effective patient management, infection and outbreak control.


Inhibition of enzyme induction in Pseudomonas aeruginosa by exogenous nucleotides.
Alkylsufatase induction in resting cell suspensions of P. aeruginosa was inhibited by exogenously supplied adenosine or by ATP (2mM). Adenine phosphate had no effect while AMP or ADP caused a slight stimulation of induction. The inhibitory effect of ATP required the presence of added Mg2+, was not reversed by cyclic-AMP (2mM), and was independent of the nature of the inducer. Of a number of other nucleoside triphosphates tested, only UTP (2mM) acted as an inhibitor of induction. These nucleotides at external concentrations of 6mM also inhibited alkysulfatase induction in actively growing cells.


Carboxyl-Rich Carbon Dots as Highly Selective and Sensitive Fluorescent Sensor for Detection of Fe3+ in Water and Lactoferrin.
As lactoferrin (LF) plays an essential role in physiological processes, the detection of LF has attracted increasing attention in the field of disease diagnosis. However, most current methods require expensive equipment, laborious pretreatment, and long processing time. In this work, carboxyl-rich carbon dots (COOH-CDs) were facilely prepared through a one-step, low-cost hydrothermal process with tartaric acid as the precursor. The COOH-CDs had abundant carboxyl on the surface and showed strong blue emission. Moreover, COOH-CDs were used as a fluorescent sensor toward Fe3+ and showed high selectivity for Fe3+ with the limit of detection (LoD) of 3.18 nM. Density functional theory (DFT) calculations were performed to reveal the mechanism of excellent performance for Fe3+ detection. Meanwhile, COOH-CDs showed no obvious effect on lactobacillus plantarum growth, which means that COOH-CDs have good biocompatibility. Due to the nontoxicity and excellent detection performance for Fe3+, COOH-CDs were employed as a fluorescent sensor toward LF and showed satisfying performance with an LoD of 0.776 µg/mL, which was better than those of the other methods.


Influence of left ventricular function on survival and mode of death after implantable defibrillator therapy (Cleveland Clinic Foundation and Montefiore Medical Center experience).
To determine the influence of left ventricular (LV) function on survival and mode of death in patients with an implantable cardioverter-defibrillator (ICD), sudden death, surgical mortality, total arrhythmia-related death, total cardiac death and total death were retrospectively evaluated in 377 consecutive patients. The outcomes were also compared between patients with an LV ejection fraction > or = 30% (214 patients, group 1) and < 30% (148 patients, group 2). Surgical mortality was 3.9% (1.8% in group 1, 7% in group 2). During the follow-up of 25 +/- 20 months, actuarial survival rates of all patients at 3 years were 96% for sudden deaths, 81% for total cardiac deaths and 74% for total mortality. When the 2 groups were compared, survival rates of groups 1 and 2 at 3 years, respectively, were 99 and 90% for sudden death (p < 0.05), 97 and 84% for sudden death and surgical mortality (p < 0.01), 94 and 80% for the total arrhythmia-related death (p < 0.001), 88 and 68% for total cardiac death (p < 0.0001), and 81 and 62% for total mortality (p < 0.002). In group 2, 73% of total cardiac deaths within 1 year were causally related to the arrhythmia. Thus, in patients with an ICD, sudden death rates were very low. However, total cardiac death and total death rates were relatively higher. The outcomes of patients with an ICD were strongly influenced by the degree of LV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)


Laryngeal Leiomyosarcoma: A Rare Case.
Laryngeal leiomyosarcoma is a rare smooth muscle malignancy of the head and neck region. Diagnosis is based on immunohistochemistry. Here we present a case of laryngeal leiomyosarcoma that was diagnosed and treated in our center, focusing on the clinical features, histological diagnosis and management of this rare disease.


Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit.
1. The effect of muscarinic antagonists considered to be selective for M1 receptors (pirenzepine) and for M2 receptors (gallamine) were studied on bronchoconstriction and bradycardia elicited by stimulation of the vagal nerves and by i.v. acetylcholine (ACh) in anaesthetized rabbits. 2. Pirenzepine was equipotent as an antagonist of ACh-induced responses at postjunctional muscarinic receptors in the heart, lung and blood vessels, whereas gallamine was at least ten times less potent at pulmonary and vascular muscarinic receptors. Thus, gallamine never caused complete inhibition of bronchoconstrictor or hypotensive responses to i.v. ACh, whereas doses of pirenzepine in excess of 1 mumol kg-1 abolished all muscarinic responses. 3. In the lung, both antagonists inhibited bronchoconstriction caused by vagal stimulation and ACh-induced bronchoconstriction to the same extent (pirenzepine, mean ED50 65 +/- 22 and, 130 +/- 28 nmol kg-1 respectively; gallamine, ED50 greater than 10,000 nmol kg-1 for both responses). Enhancement of vagally-induced bronchoconstriction was never observed. 4. In the heart, however, both pirenzepine and gallamine were ten times less potent as antagonists of vagally-induced bradycardia than of ACh-induced bradycardia. This differential blockade was unaltered by propranolol (1 mg kg-1) pretreatment. 5. It is concluded that there is no evidence for M1 or M2 muscarinic receptors in the pulmonary innervation of the rabbit and the potency of the antagonists in abolishing in abolishing vagally-induced bronchoconstriction was consistent with blockade of M3 muscarinic receptors on airway smooth muscle. 6. The results suggest that M2 muscarinic receptors may exert an inhibitory effect on transmission in the parasympathetic nerves innervating the heart in the rabbit. Blockade of such neuronal receptors would increase transmitter output to the atrial cells and explain the low potency of both antagonists in abolishing vagally-induced bradycardia in the rabbit.


Molecular mechanisms regulating axon responsiveness at the midline.
During embryonic development in bilaterally symmetric organisms, correct midline crossing is important for the proper formation of functional neural circuits. The aberrant development of neural circuits can result in multiple neurodevelopmental disorders, including horizontal gaze palsy, congenital mirror movement disorder, and autism spectrum disorder. Thus, understanding the molecular mechanisms that regulate proper axon guidance at the midline can provide insights into the pathology of neurological disorders. The signaling mechanisms that regulate midline crossing have been extensively studied in the Drosophila ventral nerve cord and the mouse embryonic spinal cord. In this review, we discuss these axon guidance mechanisms, highlighting the most recent advances in the understanding of how commissural axons switch their responsiveness from attractants to repellents during midline crossing.


Frontal-lobe involvement in spatial memory: evidence from PET, fMRI, and lesion studies.
Many studies have identified the prefrontal cortex as the brain area that is critical for spatial memory, both in humans and in other primates. Other studies, however, have failed to establish this relation. Therefore, the aim of this paper was to review the literature regarding the role of the human prefrontal lobe in spatial memory. This was done by examining the evidence obtained from neuropsychological patients and from studies using brain-imaging techniques (PET and fMRI). Evidence supporting the notion that the prefrontal cortex is extensively involved in spatial working memory was found. The majority of these studies, however, suggests that frontal-lobe involvement is not related to the type of material that is being processed (e.g., spatial vs. nonspatial), but to process-specific functions, such as encoding and retrieval. Theoretically, these functions could be linked to the central executive within Baddeley's working-memory model, or to recent theories that emphasize the various processes that play a role in working memory. Also, methodological issues were discussed. Further research is needed to enhance our understanding of the precise interaction of domain-specific and general processes.


Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene.
Iron-storage protein, ferritin plays a central role in iron metabolism. Ferritin has dual function to store iron and segregate iron for protection of iron-catalyzed reactive oxygen species. Tissue ferritin is composed of two kinds of subunits (H: heavy chain or heart-type subunit; L: light chain or liver-type subunit). Ferritin gene expression is controlled at translational level in iron-dependent manner or at transcriptional level in iron-independent manner. However, sequencing analysis of marine mammalian ferritin subunits has not yet been performed fully. The purpose of this study is to reveal cDNA-derived amino acid sequences of cetacean ferritin H and L subunits, and demonstrate the possibility of expression of these subunits, especially H subunit, by iron. Sequence analyses of cetacean ferritin H and L subunits were performed by direct sequencing of polymerase chain reaction (PCR) fragments from cDNAs generated via reverse transcription-PCR of leukocyte total RNA prepared from blood samples of six different dolphin species (Pseudorca crassidens, Lagenorhynchus obliquidens, Grampus griseus, Globicephala macrorhynchus, Tursiops truncatus, and Delphinapterus leucas). The putative iron-responsive element sequence in the 5'-untranslated region of the six different dolphin species was revealed by direct sequencing of PCR fragments obtained using leukocyte genomic DNA. Dolphin H and L subunits consist of 182 and 174 amino acids, respectively, and amino acid sequence identities of ferritin subunits among these dolphins are highly conserved (H: 99-100%, (99-->98) ; L: 98-100%). The conserved 28 bp IRE sequence was located -144 bp upstream from the initiation codon in the six different dolphin species. These results indicate that six different dolphin species have conserved ferritin sequences, and suggest that these genes are iron-dependently expressed.


Endotoxin-stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin-1 beta in vitro during infectious peritonitis.
Interleukin-1 (IL-1) release by peritoneal macrophages obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) was studied in nine patients during an infection-free period and eight patients during an infectious peritonitis, using an ELISA for IL-1 beta. Without exogenous stimulation with LPS, peritoneal macrophages from infected and uninfected patients released the same amounts of IL-1 beta, 183 +/- 40 pg ml-1 24 h-1) per 10(6) cells (means +/- SEM) and 251 +/- 96 pg ml-1, respectively. However, in response to a dose of 5 micrograms ml-1 of LPS, peritoneal macrophages released significantly more (P less than 0.005) IL-1 beta during peritonitis (6579 +/- 2793 pg ml-1 24 h-1 per 10(6) cells) compared with the infection-free period (1040 +/- 182 pg ml-1). These findings show that after microbial invasion of the peritoneal cavity, peritoneal macrophages are primed in vivo to release an increased amount of IL-1 beta in vitro after subsequent exogenous stimulation with LPS, indicating that peritoneal macrophage activation for IL-1 beta secretion occurs in steps.


Mapping the distribution of armored harvestmen (Opiliones, Laniatores) in Colombia: updated list of species, taxonomic contributions, and insight of diversity in protected areas.
Colombia is a biodiverse country with 1,486 protected areas covering almost 50 million hectares, yet little is known about the biodiversity they harbor, particularly in terms of harvestmen (Arachnida: Opiliones). This study provides a comprehensive updated summary of the armored harvestmen (Laniatores) species found in Colombia with a list of 173 nominal species, focusing on the Laniatores fauna found in protected areas and its diversity is detailed and analyzed. Maps with all records associated with ecoregions and protected areas in Colombia are presented. Additionally, three new Laniatores species are described here: Phalangodusandresisp. nov. from the department of Cundinamarca, and Ventrifurcaphallainasp. nov. and Ampycellafortunatasp. nov. from the department of Valle del Cauca; and a new family assignment is proposed for Paraphalangodus Roewer, 1915, placing it in the family Nomoclastidae. Information available on Laniatores in the National System of Protected Areas is still scarce and promoting strategies to facilitate the regulatory procedures for collecting specimens in these areas and increasing investment in basic science projects, are suggested to improve the understanding and study of the Laniatores fauna and other invertebrates in Colombia. Finally, a chronicle and timeline set of figures of species of Laniatores from Colombia, described by various authors during three periods, is given.


Iron-Doped Bimodal Mesoporous Silica Nanomaterials as Sorbents for Solid-Phase Extraction of Perfluoroalkyl Substances in Environmental Water Samples.
In this work, sorbets based on UVM-7 mesoporous silica doped with Fe were synthesized and applied to solid-phase extraction of perfluoroalkyl substances from environmental water samples. These emerging pollutants were then determined by liquid chromatography coupled with a mass spectrometry detector. Thus, Fe-UVM-7 mesoporous silica materials with different contents of iron, as well as different pore sizes (by using alkyltrimethilamonium bromide surfactants with different organic tail lengths) were synthesized, and their structure was confirmed for the first time by transmission electron microscopy, nitrogen adsorption-desorption, X-ray diffraction, and Raman spectroscopy. After comparison, Fe50-UVM-7-C12 was selected as the best material for analyte retention, and several extraction parameters were optimized regarding the loading and elution step. Once the method was developed and applied to real matrices, extraction efficiencies in the range of 61-110% were obtained for analytes with C8-C14 chain length, both perfluoroalkyl carboxylates, and perfluoroalkyl sulfonates. Likewise, limits of detection in the range of 3.0-8.1 ng L-1 were obtained for all target analytes. In the analysis of real well-water samples, no target compounds were detected. Spiked samples were analyzed in comparison to Oasis WAX cartridges, and statistically comparable results were achieved.


GAPDH S-nitrosation contributes to age-related sarcopenia through mediating apoptosis.
The age-related loss of muscle mass and muscle function known as sarcopenia is a major public health problem among older people. Recent research suggests that activation of apoptotic signaling is a critical aspect of the pathogenesis of age-related sarcopenia. However, little information exists in the literature about the apoptotic mechanism of sarcopenia in aging. Herein, we report that elevated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) S-nitrosation and apoptosis occur in sarcopenia during natural aging and that translocation of S-nitrosated GAPDH to the nucleus and S-nitrosated GAPDH-mediated apoptosis contributed to sarcopenia. The levels and sites of GAPDH S-nitrosation in muscle tissues of young, adult and old mice were studied with a quantitative S-nitrosation proteomic analysis approach. GAPDH S-nitrosation increased with aging, and the GAPDH modification sites Cys150, Cys154 and Cys245 were identified. The upregulated S-nitrosation of GAPDH relies on inducible nitric oxide synthase (iNOS) rather than enzymes involved in denitrosylation. Treatment with the iNOS inhibitor 1400W or mutation of GAPDH S-nitrosation sites alleviated apoptosis of C2C12 cells, further demonstrating that GAPDH S-nitrosation in aging contributes to sarcopenia. Taken together, these findings reveal a new cellular mechanism underlying age-related sarcopenia, and the demonstration of muscle loss mediated by iNOS-induced GAPDH S-nitrosation suggests a potential therapeutic strategy for sarcopenia.


Free light chains of immunoglobulins in the cerebrospinal fluid of human immunodeficiency virus type 1-infected patients.
The presence of immunoglobulin (Ig) free light chains (FLC) was investigated in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected patients. Intrathecal synthesis of FLC was demonstrated in 80% of the patients, even in the absence of oligoclonal Ig. The FLC patterns were characterized by restricted heterogeneity with regard to both isoelectric point and the molecular weight, and were mainly composed by dimers rather than monomers. A striking prevalence of lambda FLC was also observed. Local production of FLC can be taken as a marker of an ongoing immunopathological process within the central nervous system (CNS) in HIV-1-infected patients. A deregulation of Ig production by intrathecally activated B cells may be hypothesized.


Regulation of microglial activities by glial cell line derived neurotrophic factor.
Much attention has been paid to the ability of glial cell line-derived neurotrophic factor (GDNF) to protect neurons from neurotoxic insults in the central nervous system (CNS). However, little is known about GDNF action on CNS glia that also can express GDNF receptor systems. In this study, we examined the effects of GDNF on primary rat microglia that function as resident macrophages in the CNS and as the source of proinflammatory mediators upon activation. We found that treatment of primary rat microglia with GDNF had no effect on the secretion of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), but it increased the nitric oxide (NO) production to some extent. In addition, GDNF increased the enzymatic activity of superoxide dismutase (SOD), the gene expression of surface antigen intercellular adhesion molecule-1 (ICAM-1), the production of the integrin alpha5 subunit, and the phagocytotic capability in primary rat microglia. Furthermore, inhibition of mitogen-activated protein kinase (Erk-MAPK) in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin alpha5 production by GDNF. In vivo evidence also showed that amoeboid cells with integrin alpha5 or with ED1 immunoreactivity appeared in GDNF-treated spinal cord tissues at the lesion site 1 week post spinal cord injury (SCI). Furthermore, inhibition of Erk-MAPK in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin alpha5 production by GDNF. Taken together, our results indicate that GDNF has a positive regulatory effect on microglial activities, such as phagocytosis and the upregulation of adhesion molecules.


Association between Morphological Patterns of Myometrial Invasion and Cancer Stem Cell Markers in Endometrial Endometrioid Carcinoma.
In endometrial endometrioid adenocarcinoma (EEC), the depth of myometrial invasion (MI) is an important parameter for determining whether additional treatment is warranted. The present study investigated the association between MI patterns, cancer stem cell (CSC) phenotypes, and their clinicopathological significance in EEC. A total of 73 cases of EEC with MI were examined in this study. Haematoxylin and eosin-stained tissue specimens were analysed for MI pattern, which was categorised as infiltrating; expansile; adenomyosis (AM)-like; or microcystic, elongated, and fragmented (MELF)-type. The expression of CSC markers such as cluster of differentiation (CD)44, CD133, and Nanog1, as well as oestrogen receptor (ER) and progesterone receptor (PR) was examined by immunohistochemistry. Clinicopathological features including age, DOI, MI pattern, LVI, lymph node (LN) metastasis, disease progression, and survival outcome were recorded. Most examined cases (45/73) were International Federation of Gynecology and Obstetrics (FIGO) stage I. MI showed infiltrating (49.3%), AM-like (26.3%), MELF (15.1%), and expansile (9.6%) patterns. Tumours with the infiltrating pattern were associated with high FIGO grade (P = 0.002), reduced ER and PR, and CD44 expression (P = 0.014, 0.026, and 0.030, respectively); those with a MELF pattern showed LN metastasis (P < 0.001), lymphovascular invasion (P = 0.011), and reduced ER, CD44, and CD133 expression (P = 0.036, 0.006, and 0.016, respectively). EEC with infiltrating/MELF patterns of MI is associated with worse prognosis. These results suggest that CSC expression profiles are an unfavourable indicator of EEC.


Mating advantage of rare males in models of sexual selection.
Models of sexual selection in polygynous species of animals have been derived on the assumption that some females have preferences to mate with males with particular genotypes. The mating advantage gained by the males is always frequency-dependent because the preferred males take part in the same number of preferential matings when they are rare as when they are common; individually therefore, they mate more often when they are rare. Frequency-dependent sexual selection has been demonstrated in many experiments with Drosophila: rare males take part in a higher proportion of matings than their frequency as available mates. Ehrman and Spiess explained this phenomenon by frequency-dependence either in female preference or in male courtship. This explanation, which is difficult to interpret in behavioural terms, may not be necessary, however, because constant female preferences would entail frequency-dependent selection among the males. I show here that a simple model of constant preferences for particular phenotypes or genotypes is sufficient to explain a large body of data on frequency-dependent sexual selection in Drosophila.


The transcription factor Stat3 is dispensable for pancreatic beta-cell development and function.
The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. Gorogawa, Y. Fujitani, H. Kaneto, Y. Hazama, H. Watada, Y. Miyamoto, K. Takeda, S. Akira, M. Magnuson, Y. Yamasaki, Y. Kajimoto, M. Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. Biophys. Res. Commun. 319 (2004) 1159; Y. Cui, L. Huang, F. Elefteriou, G. Yang, J. Shelton, J. Giles, O. Oz, T. Pourbahrami, C. Lu, J. Richardson, G. Karsenty, C. Li, Essential role of STAT3 in body weight and glucose homeostasis, Mol. Cell. Biol. 24 (2004) 258]. However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. However, these mice did not develop glucose intolerance or obesity over a period of 6 months, demonstrating that Stat3 is dispensable for the generation and physiology of beta-cells. Similarly, mice that express only the Pdx1-Cre transgene display a normal physiology. In contrast, mice that expressed only the RIP-Cre transgene developed glucose intolerance as early as 6 weeks of age. The finding that RIP-Cre transgenic mice in a C57B/6 dominated background develop glucose intolerance is important as this line has been used in several studies.


Developing an eczema action plan.
As physicians, we spend time learning about diseases and their management. The key to successful outcomes is the involvement of patients and their families in the care of the conditions for which they seek our assistance. For atopic dermatitis (AD), all patients require frequent emollients for xerotic skin and care of the inflammation, which comes and goes frequently. The levels of care required vary by time and patient. Younger patients require the help of parents or other family members. A keen understanding of the timing and appropriate use of the various treatment modalities is required and is often confusing. Action plans, as used in the care of asthma, for instance, can be effectively integrated into the overall care instructions for AD and have been indispensable for many of my patients and their families. They are one concrete method for patient/family engagement in the overall care planning. The action plans can certainly be translated into languages appropriate for any practice environment. The following brief summary should be of use to those professionals considering the use of this technique.


Gentamicin disposition in young and elderly patients with various degrees of renal function.
The effect of aging on the total body clearance, volume of distribution, and half-life of gentamicin was examined in 99 febrile patients with various degrees of renal function. In the 50 patients who were 18 to 64 years old, clearance of gentamicin was 79.0 +/- 27.0 mL/min (mean +/- standard deviation), creatinine clearance was 98.6 +/- 33.3 mL/min, volume of distribution was 0.242 +/- 0.077 L/kg, and half-life was 2.63 +/- 0.90 hours. In the 49 patients who were 65 to 90 years old, these values were 36.9 +/- 16.3 mL/min, 51.2 +/- 21.2 mL/min, 0.244 +/- 0.102 L/kg, and 5.80 +/- 4.13 hours. Significant differences were observed between the two groups for all parameters except volume of distribution. Linear regression revealed good correlations between the disposition characteristics (clearance and elimination-rate constant) of gentamicin and age as well as creatinine clearance. However, there was no apparent relationship between the ratio of gentamicin clearance to creatinine clearance and age (r = .0731). These findings suggest that the disposition of gentamicin is independent of age but dependent on renal function.


Spontaneous and reflex activity of paraventricular nucleus units in cycling and lactating rats.
Extracellular recording of paraventricular neurones after electrical stimulation of the neurohypophysis reveals three cell types: type I cells, invaded by an antidromic action potential; type II cells, whose evoked response is orthodromic; and type III cells, which do not respond to stimulation. During the oestrous cycle of the rat, type I cells are the only ones in the paraventricular nucleus (PVN) whose spontaneous activity (expressed in number of action potentials per second) varies. It is significantly higher during lactation (3.6 "/- 0.6) and pro-oestrus (3.4 "/- 0.5) than during oestrus (2.0 +/- 0.5), metoestrus (1.2 +/- 0.3) and dioestrus (1.5 +/- 0.4). There are significantly more phasic units during prooestrus. The mean spontaneous firing rate of type II and III cells, remain unchanged. The reflex activity of those neurones was studied. Vaginal dilatation, which evokes a release of oxytocin31, increases the activity of a small percentage of type I cells, but there are no differences in this response at different stages of the cycle and lactation. Silent and phasic type I units are never activated. Only the evoked activity of type III cells is affected by the endocrine state. These results are discussed in the light of the known or hypothetical roles of these different cells.


Synaptic structural changes during development and aging.
Although a great deal is known about the development of synaptic number, comparatively little is known about the effects of development, and particularly aging, on the structure of the synapse. The present study examined synaptic structure in the molecular layer of the motor-sensory neocortex during early development (postnatal days (P) 1, 3, 5, 7, 10, 15, 20, 30), adulthood (P60, 90), and old age (28 months). Tissue was stained with osmium tetroxide (osmium) or ethanol phosphotungstic acid and the following synaptic characteristics were quantified: (1) presynaptic element length, area, thickness, maximal projection height and smoothness, and number and size of vesicles adjacent to the presynaptic element; (2) postsynaptic element length, area, and thickness; and (3) cleft width. There is an early developmental increase in synaptic element length, followed by an increase in thickness into adulthood. During development the height and width of the presynaptic dense projections increase, after which they remain stable. While the number of adjacent synaptic vesicles increases throughout the lifespan, there is a parallel decrease in their size. During the period of rapid synaptogenesis in this brain region there are no decreases in any of the synaptic structural parameters examined, indicating that newly generated synapses are either formed the same size as the existing mature synapses, or are extremely plastic and grow very rapidly. Unlike age-associated changes in synaptic number, no changes were found in synaptic structure during aging.


The effect of the elderly and child care on household carbon emissions.
The aim of this work is to investigate the different implications in terms of the elderly and child care on household carbon emissions in China. We estimate the effect of family structure on household carbon emissions in the 2018 China Family Panel Studies (CFPS), by means of the STIRPAT model. The results indicate that significant differences exist between the effect of the elderly and child care on each household's carbon emissions. Moreover, there is a negative effect between the elderly and household carbon emissions with an elasticity coefficient of -0.029, and a positive effect between children and household carbon emissions with an elasticity coefficient of 0.008. Interestingly, the elderly and children have an interactive effect on carbon emissions except for housing carbon emissions. To be specific, the elderly and child care have a mutual inhibition effect on the health carbon emissions of household, whereas they have a mutually reinforcing effect on other carbon emissions. Low carbon emissions paths in household should be urgently explored, and deliberate policy action is required to achieve carbon emissions reduction.


Rare MLL-ELL fusion transcripts in childhood acute myeloid leukemia-association with young age and myeloid sarcomas?
The chromosomal translocation t(11;19)(q23;p13) with a breakpoint within subband 19p13.1 is found mainly in acute myeloid leukemia (AML) and results in the MLL-ELL fusion gene. Variations in the structure of MLL-ELL seem to influence the leukemogenic potency of the fusion in vivo and may lie behind differences in clinical features. The number of cases reported so far is very limited and the addition of more information about MLL-ELL variants is essential if the possible clinical significance of rare fusions is to be determined. Cytogenetic and molecular genetic analyses were done on the bone marrow cells of a 20-month-old boy with an unusual form of myelomonocytic AML with multiple myeloid sarcomas infiltrating bone and soft tissues. The G-banding analysis together with FISH yielded the karyotype 47,XY, +6,t(8;19;11)(q24;p13;q23). FISH analysis also demonstrated that MLL was split. RNA-sequencing showed that the translocation had generated an MLL-ELL chimera in which exon 9 of MLL (nt 4241 in sequence with accession number NM_005933.3) was fused to exon 6 of ELL (nt 817 in sequence with accession number NM_006532.3). RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. Based on our findings and information on a few previously reported patients, we speculate that young age, myelomonoblastic AML, and the presence of extramedullary disease may be typical of children with rare MLL-ELL fusion transcripts.


A roadmap for a comprehensive diagnostic approach to fine needle cytology of lymph node metastases.
Fine needle cytology (FNC) is widely used as a first-line procedure in the diagnostic algorithm of lymphadenopathies. In a metastatic setting, a first-line diagnostic approach identifies non-haematopoietic malignancy; however, cytopathologists could also provide a second diagnostic level, identifying the origin of the primary tumour. This paper outlines a comprehensive and practical approach to the cytological diagnosis of lymph node metastases. Cytological diagnoses of lymph node metastases performed over a 10-year period were selected and divided into two groups. The first group, labelled "oncological," comprised patients with a previous history of malignancy; the second group, labelled "naïve," included patients with no relevant history. Pathology records were retrieved to record microscopic findings, namely, background appearance, group architecture, and specific cell features; data from cell block (CB) preparations were also collected. Overall, 982 cases were selected: 497 cases (50.61%) in the naïve group, and 485 (49.39%) in the oncological group. Overall, a second diagnostic level was achieved in 834/982 cases (84.92%); cases diagnosed as carcinoma not otherwise specified were more frequent in the naïve group than in the oncological group (17.51% vs. 8.04%, P < 0.01). Notably, although CB material was available in only 44.87% of the naïve cases, we were able to achieve a second diagnostic level thanks to the integration of clinical and cytomorphological findings, plus lymph node topography, in 82.49% of the cases. Our results confirmed that in a metastatic setting, FNC can reliably lead to the identification of the origin of the primary tumour.


Changes in myocardial oxygen consumption and coronary sinus blood flow before and after resection of left ventricular aneurysm after myocardial infarction.
The patients in this study consisted of eight men who underwent resection of left ventricular aneurysm. Right and left heart catheterization at rest and measurement of coronary sinus blood flow by continuous thermodilution were performed preoperatively and an average of 6 months after the operation. Coronary sinus blood flow decreased significantly from 161 to 118 ml/min and myocardial oxygen consumption decreased significantly from 17.2 to 10.5 ml/min postoperatively. Cardiac index increased postoperatively. Ejection fraction increased from 0.31 to 0.49 and mean velocity of circumferential fiber shortening significantly increased from 0.53 to 1.0 circ/sec postoperatively. Left ventricular end-diastolic volume decreased significantly from 166 to 120 ml/m2 postoperatively. The mean systolic circumferential tension significantly decreased postoperatively. We believe that the decrease in wall tension postoperatively brought about the reduction in myocardial oxygen consumption. Thus the high wall tension and myocardial oxygen demand, present preoperatively, were improved postoperatively, with a resultant lowering of oxygen consumption and equivalent or better left ventricular function.


Special Issue "Chikungunya Virus and Emerging Alphaviruses".
Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes, has experienced a recent re-emergence in various regions of the world, leading to large-scale outbreaks [...].


Nucleation-mediated growth of chiral 3D organic-inorganic perovskite single crystals.
Although their zero- to two-dimensional counterparts are well known, three-dimensional chiral hybrid organic-inorganic perovskite single crystals have remained difficult because they contain no chiral components and their crystal phases belong to centrosymmetric achiral point groups. Here we report a general approach to grow single-crystalline 3D lead halide perovskites with chiroptical activity. Taking MAPbBr3 (MA, methylammonium) perovskite as a representative example, whereas achiral MAPbBr3 crystallized from precursors in solution by inverse temperature crystallization method, the addition of micro- or nanoparticles as nucleating agents promoted the formation of chiral crystals under a near equilibrium state. Experimental characterization supported by calculations showed that the chirality of the 3D APbX3 (where A is an ammonium ion and X is Cl, Br or mixed Cl-Br or Br-I) perovskites arises from chiral patterns of the A-site cations and their interaction with the [PbX6]4- octahedra in the perovskite structure. The chiral structure obeys the lowest-energy principle and thereby thermodynamically stable. The chiral 3D hybrid organic-inorganic perovskites served in a circularly polarized light photodetector prototype successfully.


Impact of changes in social anxiety on social functioning and quality of life in outpatients with schizophrenia: A naturalistic longitudinal study.
The prevalence of comorbid social anxiety disorder among patients with schizophrenia is currently attracting attention, and symptoms of social anxiety are reportedly associated with various clinical features. However, the contribution of social anxiety to social functioning and quality of life (QOL) over time remains obscure. The aim of this study was to examine the impact of changes in social anxiety symptoms on social functioning and QOL among outpatients with schizophrenia. Of the 207 outpatients who were eligible at baseline, 118 patients agreed with and completed a follow-up investigation at least 1 year (695.8 days on average) after the baseline study. Stepwise multiple regressions examining the change in social functioning using demographic data and changes in clinical variables as explanatory variables demonstrated that the changes in social anxiety and general psychopathology contributed to the change in the Social Functioning Scale, while the changes in clinical severity and negative symptoms contributed to the change in the Global Assessment of Functioning scale. Stepwise multiple regressions for the change in QOL demonstrated that the changes in social anxiety and depression contributed to the change in the World Health Organization QOL scale, Brief version, and the changes in social anxiety and positive symptoms contributed to the Subjective Well-being Under Neuroleptic Drug Treatment, Short Form. The results revealed that the changes in social anxiety symptoms were significantly associated with the change in functional outcome among patients with schizophrenia. Treatments targeting social anxiety seem to be key to achieving a full recovery in patients with schizophrenia.


Regulation of Notch Signaling Through Intracellular Transport.
The highly conserved Notch-signaling pathway performs a central role in cell differentiation, survival, and proliferation. A major mechanism by which cells modulate signaling is by controlling the intracellular transport itinerary of Notch. Indeed, Notch removal from the cell surface and its targeting to the lysosome for degradation is one way in which Notch activity is downregulated since it limits receptor exposure to ligand. In contrast, Notch-signaling capacity is maintained through repeated rounds of receptor recycling and redelivery of Notch to the cell surface from endosomal stores. This review discusses the molecular mechanisms by which Notch transit through the endosome is controlled and how various intracellular sorting decisions are thought to impact signaling activity.


Predicting prognosis based on the shape of the left ventricular cavity in dilated cardiomyopathy: analysis using rate of improvement in the circle index.
To elucidate the relation between a quantitative measure of the shape of the left ventricular cavity, cardiac function, and prognosis in patients with dilated cardiomyopathy (DCM). The hearts of 20 healthy individuals and 18 patients with DCM were evaluated. Participants were aged 48.5 ± 5.0 years. On the basis of end-systolic four-chamber view echocardiograms, the endocardium of the left ventricle was traced and the resulting curve was segmented using 100 points. A line tangential to the curve was then drawn at each point, and the angle between two adjacent tangential lines was calculated. The deviation of these angles was designated as the circle index. The circle index and hemodynamic findings in patients with DCM were compared, and the rate of improvement in the circle index in these cases of DCM was determined. These patients were then placed into one of two groups: group R (11 patients), those with improvement rates of 10% or higher at time of discharge; and group NR (seven patients), those with rates less than 10%. Diuretic (furosemide) use, New York Heart Association (NYHA) classification, and readmission rate for the two groups were compared 2 years after discharge. The circle index was 2.7 ± 0.9 in the DCM group and 17.5 ± 4.2 in the healthy group (P < 0.01). The circle index in the DCM group was correlated with pulmonary capillary wedge pressure (r(2) = 0.42). Use of furosemide was unchanged in group R 2 years after discharge, but had increased for all patients in group NR. All cases in group R were classified as NYHA I 2 years after discharge. In group NR, in contrast, although all cases were classified as NYHA I at discharge, five of seven cases had deteriorated to NYHA III-IV 2 years later and were readmitted to hospital. There appears to be a quantifiable correlation between the circularity of the left ventricular cavity and the circle index. This suggests that rate of improvement after treatment for heart failure could predict prognosis in patients with DCM.


Chorionic villi sampling: clinical experience, immediate complications, and patient attitudes.
To develop chorionic villi sampling as a procedure for prenatal diagnosis, a pilot study was undertaken to perfect the obstetric and laboratory techniques, to evaluate our success with the procedure in continuing pregnancies, and to assess the attitudes of potential users of the procedure. Women about to have elective first-trimester abortions for nongenetic reasons were enrolled in the first phase of the study. Of the patients with a positive pregnancy test, 12.4% were found to have a nonviable pregnancy on ultrasound examination. Samples adequate for cytogenetic analysis were obtained in 130 of the 155 remaining cases, and the success rate was 93% in the 100 most recent cases. Direct cytogenetic analysis was undertaken in those cases successfully sampled, and karyotypes could be prepared in 97%. Immediate complications occurred in 5% of the pregnancies. Eight women at risk of bearing a child with a genetic defect had diagnostic chorionic villi sampling. Cytogenetic analysis was performed successfully on all of them. One had an induced abortion following the procedure because of the fetal diagnosis (a male with a 50% risk of Duchenne's muscular dystrophy). The other pregnancies are continuing uneventfully at 22 to 35 weeks' gestation. Finally, from preliminary analysis of our survey of potential users it appears that women 35 years old or over would prefer chorionic villi sampling to amniocentesis if the risks of the sampling were known to be low.


An electron microscopic study of the adductor externus superficialis muscle associated with the venom gland of the cobra (Naja naja).
The adductor externus superficialis muscle closely envelops the venom gland in the cobra (Naja naja). Only twitch fibres are present in the muscle, supporting the view that the muscle is concerned with the rapid evacuation of venom. 'Satellite' cells are readily observed in relation to the muscle fibres.


Effect of kininogen on the activity of the kallikreinogen-kallikrein system of human blood serum.
In experiments with kallikreinogen, kallikrein and kininogen preparations from human blood serum partially purified on QAE-Sephadex A-50, CM-Sephadex and Sephadex G-200 it was established that N-benzoyl-L-arginine ethyl ester (BAEE)-esterase activity of kallikrein and the process of autoactivation of kallikreinogen are inhibited by kininogen, especially by its high-molecular form.


New Longitudinal Component of the RENAL Nephrometry Score for Predicting the Operative Complexity in Transperitoneal Robot-Assisted Partial Nephrectomy.
Background: In transperitoneal robot-assisted partial nephrectomy (RAPN), an L score of 3 points according to the RENAL nephrometry scoring system does not necessarily denote operative complexity. This study aimed to assess the efficacy of the newly defined longitudinal component to analyze the operative complexity of RAPN. Materials and Methods: We retrospectively analyzed transperitoneal RAPNs performed by a single experienced surgeon for renal tumors between 2017 and 2020. L component was defined as L'1 for midlocated tumors, L'2 for >50% below the polar line, and L'3 for >50% above the polar line. Multivariate regression analysis was performed to test associations between prolonged console time and preoperative factors. The perioperative outcomes were compared among the three cohorts of L' components using propensity score matching: L'1 vs L'3 and L'1 vs L'2. Results: A total of 220 cases (L'1: 107, L'2: 65, L'3: 48) were analyzed. The median console time was prolonged (>130 minutes) in 55 patients (median 108, interquartile range: 90-130 minutes). Longitudinal location (L'3 odds ratio [OR]: 2.93, p = 0.01; L'2 OR: 2.32, p = 0.04), high Mayo adhesive probability score (p = 0.001), multiple renal arteries (p = 0.03), and large size (p = 0.04) were significantly associated with prolonged console time. After matching, 26 cases of L'1 and L'3 and 43 cases of L'1 and L'2 were selected. Console time (108 minutes vs 132 minutes, p = 0.017) and warm ischemia time (17 minutes vs 22 minutes, p = 0.03) were significantly longer in L'3 than in L'1. The difference in console time between L'1 and L'2 was not statistically significant (100 minutes vs 111 minutes, p = 0.08). Conclusion: In the new longitudinal assessment, upper location predicted prolonged console time compared with a middle or lower location. The L' component may help preoperatively assess operative complexity.


Effects of gender nonconformity and biological sex on the relationship between sexual orientation microaggressions and anxiety and depressive symptoms among lesbian, gay, and bisexual Taiwanese young adults: A moderated-moderation study.
Sexual orientation microaggressions (SOMs) may negatively affect lesbian, gay, and bisexual (LGB) individuals' mental health. However, the moderating effects of gender nonconformity and biological sex on the relationship between SOMs and anxiety and depressive symptoms has never been examined. We evaluated the moderating effect of gender nonconformity on the association of SOMs with anxiety and depressive symptoms among LGB young male and female adults. We hypothesized that the associations of SOMs with anxiety and depressive symptoms weakened with increasing gender nonconformity among gay and bisexual men but strengthened with increasing gender nonconformity among lesbian and bisexual women. In total, 1000 self-identified LGB young adult individuals participated in the study. The experience of sexual orientation microaggression was assessed using the Sexual Orientation Microaggression Inventory, anxiety was assessed using the State subscale on the State-Trait Anxiety Inventory, and depression was assessed using the Center for Epidemiological Studies-Depression Scale. The two-way moderation models stratified by sex examined the moderating effects of gender nonconformity on the association between SOMs and anxiety symptoms in the male and female participants. The three-way moderated moderation models were used to determine whether gender nonconformity and sex jointly moderated the associations between SOMs and anxiety and depressive symptoms. In the two-way moderation models stratified by sex, gender nonconformity exerted opposite moderating effects on the association between SOMs and anxiety and depressive symptoms in the male and female participants. For the male participants, the association between SOMs and anxiety (β = -0.08) and depressive symptoms (β = -0.09) weakened with increasing gender nonconformity. For the female participants, the association between SOMs and anxiety (β = 0.08) and depressive symptoms (β = 0.13) strengthened with increasing gender nonconformity. The three-way moderated moderation models further confirmed that sex moderated the moderating effects of gender nonconformity on the associations between SOM and anxiety (β = -0.16, p = .047) and depressive symptoms (β = -0.22, p < .001). The cross-sectional study design limited the inferences that could be made concerning the temporal relationship between SOMs and mental health problems. The association between SOMs and anxiety and depressive symptoms weakened with increasing gender nonconformity in gay and bisexual men, whereas the association between SOMs and anxiety and depressive symptoms strengthened with increasing gender nonconformity in lesbian and bisexual women.


Novel SNP based analysis of genetic diversity in Polygonatum verticillatum Linn. across Indian Himalayas.
Polygonatum verticillatum Linn. is an endangered medicinal herb from Himalayas whose rhizomes have recently been used to curate symptoms of COVID-19. During present investigation, a gene bank of P. verticillatum was established at High Altitude Herbal Garden of Forest Research Institute, Dehradun at Chakrata, at 2600 m amsl with germplasm collected from different states and union territory of India including Himachal Pradesh, Sikkim, Uttarakhand and Jammu and Kashmir covering a wide range of geographical locations from an altitude of 1800 to 3600 m amsl. Genotyping by sequencing was applied to a set of 66 accessions of P. verticillatum to identify genome-wide high quality single nucleotide polymorphisms (SNPs) for analysis of genetic diversity. Neighbour-joining tree created from the distance matrix data grouped the genotypes into five distinct clusters. The results of principal coordinate analysis and Cluster analysis overlapped to identify Narkanda, Shimla (Himachal Pradesh) and Sunil village, Chamoli (Uttarakhand) as the regions with undisturbed, highly diverse natural populations of P. verticillatum. The species displayed little congruence in terms of genetic similarities with altitudinal range. This investigation is first of its kind on generation and utilization of SNPs to analyse genetic diversity in P. verticillatum with a very vivid sample collection across the entire Himalayan range in India. The online version contains supplementary material available at 10.1007/s13205-023-03654-4.


Novel OPN1LW/OPN1MW deletion mutations in 2 Japanese families with blue cone monochromacy.
Blue cone monochromacy (BCM) is caused by the lack of expression of the normal proteins encoded by the OPN1LW and OPN1MW genes, resulting in the absence of red and green cone sensitivities. We analyzed two cases of BCM in two different families and identified deletion mutations in the locus control region upstream of the two genes. Deletion breakpoints were determined to an accuracy of one base for both cases.


Concordance of Ureaplasma urealyticum and Mycoplasma hominis in infertile couples: impact on semen parameters.
To assess the relationship between mycoplasma infection and human infertility, we determined the concordance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) detection in infertile and fertile couples, and assessed semen parameters in both groups. Fifty infertile couples without a female factor attending a fertility clinic and 48 fertile couples were randomly screened for UU and MH. The concordance between partners was compared between the fertile and infertile groups. Semen and endocervical specimens were evaluated using the commercially available Mycofast Evolution2 test. UU was detected in 24 semen specimens (48%) from the infertile men, in 12 specimens from fertile men (25%), in 20 endocervical specimens from infertile women (40%), and 11 from fertile women (22.9%). UU was detected higher in infertile men than in fertile men (P = .022). The concordance of UU was higher in infertile couples (32%) than in fertile couples (12.5%, P = .022). The concordance of MH between male and female partners in the 2 groups did not differ significantly. The mean values of total motility, progressive motility, normal morphology, vitality, and total motile sperm count were significantly lower in sperm from infertile men than from fertile men. Progressive motility and vitality were significantly lower in UU-positive men than in men without UU, and low total motility and total motile sperm count were significantly related to the presence of MH. Clinicians should consider the roles of UU and MH in infertility and routinely screen infertile couples for the presence of these mycoplasma species.


Colposuspension in girls: clinical and urodynamic aspects.
To investigate the effect of colposuspension on bladder function and urinary incontinence in girls with structural stress incontinence. A Burch colposuspension was performed in 26 incontinent girls for congenital bladder neck insufficiency (10), incontinence after urethrotomy (seven), hypospadias (five) and ectopic ureterocele (four). The indication for surgery was failure of conservative therapy (consisting of cognitive and biofeedback bladder training, physical therapy and/or antimuscarinic drugs in 23 children) and a severe anatomical defect of the bladder outlet in three. Colposuspension was combined with reconstruction of the distal urethra in three patients and of the bladder neck in seven. All girls had urodynamic tests before and after colposuspension. After surgery 14 of the 26 patients (54%) were completely dry, four (15%) had improved and eight (31%) still had incontinence requiring pads. In 17 patients (65%) additional conservative therapy was given and three (12%) had additional surgery. After a median follow-up of 62 months, 65% were completely dry, 19% had improved and 15% were incontinent. Of 25 patients who had recurrent urinary tract infections before colposuspension, 14 had none afterwards. Bladder overactivity in 10 patients before colposuspension resolved in five and de novo overactivity was detected in four. In a selected group of girls with structural urinary incontinence, Burch colposuspension can be used when medical treatment, cognitive and biofeedback bladder training fail. It is reasonably effective for resolving incontinence and safe for bladder function.


Prenatal diagnosis of iniencephaly.
Iniencephaly is characterized by a variable deficit of the occipital bones, resulting in an enlarged foramen magnum; partial or total absence of cervical and thoracic vertebrae with an irregular fusion of those present, accompanied by incomplete closure of the vertebral arches and/or bodies; significant shortening of the spinal column due to marked lordosis and hyperextension of the malformed cervicothoracic spine; and an upward-turned face and mandibular skin directly continuous with that of the chest due to the lack of neck. This article provides a comprehensive review of the reported cases of prenatally detected iniencephaly, including prenatal diagnosis, associated malformations, associated chromosomal abnormalities, and differential diagnosis. Prenatal diagnosis of a neural tube defect involving a body defect in the occiput and rachischisis of the cervical and thoracic spine with retroflexion of the head should raise the suspicion of iniencephaly. Iniencephaly may be associated with craniorachischisis and other structural anomalies. Prenatal diagnosis of non-isolated iniencephaly and craniorachischisis should alert one to the possibility of chromosomal abnormalities and prompt a cytogenetic investigation.


Virtual reality and serious game therapy for post-stroke individuals: A preliminary study with humanized rehabilitation approach protocol.
The current study proposed the development and preliminary validation of a humanized training approach for upper limb rehabilitation of chronic post-stroke individuals, using serious game (SG) and virtual reality (VR) technologies. Ten individuals with chronic stroke participated in the study. Accompanied by a health professional, 15 sessions of the SG were performed in a laboratory, in a humanized way, lasting between 30 and 45 min each. The assessments were made pre- and post-intervention with the SG, and the following parameters were evaluated (considering the elbow joint): Modified Ashworth Scale (MAS), range of movement (ROM) and tonic stretch reflex threshold (TSRT). Global measures such as quality of life (QOL) were also assessed by the Stroke-Specific Quality of Life Scale (SSQL), Brunnstrom Recovery Scale (BRS) and General Health Questionnaire (GHQ-28). The following tests were applied to verify statistically significant differences: Shapiro-Wilk test, t-test, and Wilcoxon-Mann-Whitney test. The parameters ROM, TSRT, BRS, and SSQL showed statistically significant differences between pre- and post-intervention (p < 0.01). The ROM increase was about 8%. The objective evaluation of spasticity (provided by the TRST) showed an increase of 28% over the average pre- and post-intervention values. Three participants showed decreased resistance to passive stretching according to the results of the MAS, and seven participants moved to the next stage of the BRS. For QOL, the scores indicated around 20% of post-intervention improvement. The intervention had no adverse effects, showed a high degree of compliance, provided increased ROM, improved QOL, reduced spasticity and allowed these individuals the opportunity to test a promising technology for upper limb rehabilitation with emphasis in humanized aspects of therapy.


Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson's disease.
Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment. In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson's disease' risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations. We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson's disease (OR = 0.59; 95%CI = 0.38-0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15-0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events. Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment.


Effect of high-intensity exercise and high-fat diet on lipid metabolism in the liver of rats.
This study investigated the effects of high-intensity exercise (Ex) and high dietary fat intake on lipid metabolism in the liver of rats. Male Sprague-Dawley rats were randomly assigned to one of the four groups (n=10 per group) that were maintained on a normal diet (ND) or high-fat diet (HFD) consisting of 30% fat (w/w), with or without exercise on a treadmill at 30 m/min and 8% grade) for 4 weeks (i.e., ND, ND+Ex, HFD, and HFD+Ex groups). Body weight (p<.001), total plasma cholesterol (TC) (p<.001), triglyceride (TG) (p<.05), and liver TG levels (p<.05) were increased in the HFD group relative to the ND groups, and serum glucose (p<.05), insulin (p<.05), homeostatic model assessment of insulin resistance (HOMA-IR) (p<.01), and liver TG levels (p<.01) were also higher in the HFD group compared to the ND+Ex group. Plasma free fatty acid was elevated in the HFD+Ex group compared to the HFD group (p<.01). With the exception of acetyl coenzyme A carboxylase, the expression of lipid metabolism-related genes in the liver was altered in the Ex groups compared to the control group (p<.05), with genes involved in lipolysis specifically up regulated in the HFD+Ex group compared to the other groups. Vigorous exercise may increase glucose utilization and fat oxidation by activating genes in the liver that are associated with lipid metabolism compared to that in animals consuming a HFD without exercise. Therefore, high intensity exercise can be considered to counter the adverse effects of high dietary fat intake.


Antimicrobial use and resistance in Democratic Republic of Congo: Implications and recommendations; A mini review.
Antimicrobial resistance is a public health problem in the Democratic Republic of Congo and it occurs when pathogens (bacteria, viruses and parasites) no longer respond to antimicrobial drugs. So, their treatment becomes ineffective and complex increasing the risk the spread of infectious and opportunistic diseases and producing serious forms of these infections leading to a high number of deaths. It is important to put in place effective methods and materials for the prevention and treatment of infections resistant to antimicrobial drugs, to provide improved access to quality antimicrobials and to reduce the number of treatment failures. Increasing levels of resistance have significant economic consequences and third-line treatments become much more expensive than first- and second-line treatments. As antimicrobial resistance is a complex health problem that requires a coordinated multisector approach, it is important to intensify innovation in operational research and the development of new antimicrobial drugs. Surveillance remains a valuable tool in the fight against antimicrobial resistance in the Democratic Republic of Congo, as it helps to detect resistant infections and allows corrective decisions to be made, this surveillance guides policy recommendations and the monitoring of use and treatment and abuse of antibiotics. Our study aimed to show the importance of establishment of national plans for the fight against antimicrobial resistance by installing laboratories and monitoring sites in order to reduce the risk and rate of deaths due to antimicrobial resistance in the Demographic republic of Congo.


Identification of bile canalicular cell surface antigen HAM.4 as dipeptidyl peptidase IV (DPPIV) and characterization of its role in hepatic regeneration after partial hepatectomy in rats.
Dipeptidyl peptidase IV (DPPIV) has been implicated in the control of cell growth and differentiation. A rat hepatocyte membrane antigen recognized by a monoclonal antibody (HAM.4) has now been shown to be identical to DPPIV by immunoblot analysis and amino acid sequencing. The amounts of DPPIV immunoreactive protein and enzymatic activity in serum increased in a manner independent of de novo protein synthesis, and without any biochemical or immunohistochemical changes in hepatic DPPIV, during liver regeneration after partial hepatectomy in rats. DPPIV purified from serum by HAM.4 antibody-based affinity chromatography lacked the NH2-terminal 36 amino acids of the membrane-bound enzyme, suggesting that proteolytic cleavage may mediate the release of DPPIV into serum. No significant differences in the restoration of liver mass or in hepatic DNA synthesis were apparent between DPPIV-deficient and normal rats after partial hepatectomy, suggesting that DPPIV may not be essential for hepatic regeneration.


Renal outcomes associated with glucose-lowering agents: Systematic review and meta-analysis of randomized outcome trials.
Although the clinical questions of the recent glucose-lowering trials are principally oriented towards preventing macrovascular events, an updated review regarding renal outcome prevention is lacking. We assessed the impact of different antihyperglycemic classes on kidney damage progression. A systematic review and meta-analysis was performed by searching PubMed, Cochrane Collaboration Library, Medline, and previous overviews through June 2021 (any language) for earlier and contemporary glucose-lowering trials, including patients with, but not limited to, type 2 diabetes mellitus vs. placebo or less intense treatment. Incidences of kidney function worsening and macroalbuminuria development was extracted, and risk ratios and 95% confidence intervals (CI) under the random-effects model were calculated. The association between outcome reductions and glycohemoglobin (HBA1c) reductions was investigated through the meta-regression analyses. Among 27 eligible trials (n = 198,532 patients) an averaged HBA1c reduction of 0.6 ± 0.3% was followed by a reduction of 17% (95% CI, 8-25%) in worsening of kidney function, and of 25% (95% CI, 19-32%) in macroalbuminuria. Analog of human glucagon-like peptide 1 (GLP1)-agonists, and sodium-glucose cotransporter (SGLT2)-inhibitors, considered separately, compared with placebo, were associated with a significant reduction of both renal outcomes, at variance with dipeptidyl peptidase 4 (DPP4)-inhibitors, where no outcome change was observed. Logarithmic risk ratios of macroalbuminuria were related to HBA1c reductions, in contrast to the worsening of kidney function related to systolic blood pressure reduction. Worsening of kidney function and macroalbuminuria development were reduced following glucose-lowering. GLP1 agonists and SGLPT2 inhibitors were associated with protection against both outcomes, while DPP4 inhibitors do not provide renal protection.


The role of plasma secretin during starvation in dogs.
Plasma secretin levels were measured during a 72-hour starvation period in dogs. Plasma secretin rose significantly and insulin levels fell significantly during starvation. Intravenous glucose loading at the end of the 72-hour starvation period suppressed plasma secretin and free fatty acid levels with a concomitant rise of glucose and insulin levels. These findings suggest that secretin might be regulated by plasma glucose and insulin levels and might play a role in lipolysis during starvation.


Affinity-based Protein Surface Pattern Formation by Ligand Self-Selection from Mixed Protein Solutions.
Photolithographically prepared surface patterns of two affinity ligands (biotin and chloroalkane) specific for two proteins (streptavidin and HaloTag®, respectively) are used to spontaneously form high-fidelity surface patterns of the two proteins from their mixed solution. High affinity protein-surface self-selection onto patterned ligands on surfaces exhibiting low non-specific adsorption rapidly yields the patterned protein surfaces. Fluorescence images after protein immobilization show high specificity of the target proteins to their respective surface patterned ligands. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging further supports the chemical specificity of streptavidin and HaloTag® for their surface patterned ligands from mixed protein solutions. However, ToF-SIMS did detect some non-specific adsorption of bovine serum albumin, a masking protein present in excess in the adsorbing solutions, on the patterned surfaces. Protein amino acid composition, surface coverage, density and orientation are important parameters that determine the relative ToF-SIMS fragmentation pattern yields. ToF-SIMS amino acid-derived ion fragment yields summed to produce surface images can reliably determine which patterned surface regions contain bound proteins, but do not readily discriminate between different co-planar protein regions. Principal component analysis (PCA) of these ToF-SIMS data, however, improves discrimination of ions specific to each protein, facilitating surface pattern discrimination and contrast.


Pharmacological Treatments for Fragile X Syndrome Based on Synaptic Dysfunction.
Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. In FXS, synaptic dysfunction alters the excitation-inhibition ratio, dysregulating molecular and cellular processes underlying cognition, learning, memory, and social behavior. Decades of research have yielded important hypotheses that could explain, at least in part, the development of these neurological disorders in FXS patients. However, the main goal of translating lab research in animal models to pharmacological treatments in the clinic has been so far largely unsuccessful, leaving FXS a still incurable disease. In this concise review, we summarize and analyze the main hypotheses proposed to explain synaptic dysregulation in FXS, by reviewing the scientific evidence that led to pharmaceutical clinical trials and their outcome.


[Mycoplasma pneumoniae infection associated with ectodermosis pluriorificialis: a report of two cases].
Two children (4 and 12 years old) presented with a Stevens-Johnson syndrome. The symptoms and their evolution were remarkably similar. In both cases, a Mycoplasma pneumoniae infection was suspected after a serolgic study. This etiology, still unfamiliar, must be suspected in presence of severe stomatitis in children.


[Osteotomies of the forearm in the treatment of ulnar dysmelia (author's transl)].
The syndrome and classification of ulnadysmelia--which shows considerable analogy to fibuladysmelia--is described on the basis of two cases. The therapy of the milder form of this deformation which includes our two patients is discussed. Correction osteotomy of the bones of both forearms with excision of the radial head is recommended for inveterate cases. In younger children, a result which is both cosmetically and functionally successful can be achieved by lenghtening osteotomy of the ulna. The operation is to be repeated if necessary.


Nine new tropane alkaloids from Datura stramonium L. identified by GC/MS.
Sixty seven tropane alkaloids were identified in the organs of Datura stramonium L. by GC/MS. Nine new tropane alkaloids, 3,7-dihydroxy-6-propionyloxytropane, 6,7-dehydro-3-tigloyloxytropane, 3-tigloyloxy-6,7-epoxytropane, 3,7-dihydroxy-6-(2'-methylbutyryloxy)tropane, 6,7-dehydroapoatropine, 3-(3'-methoxytropoyloxy)tropane, 3-tigloyloxy-6-isobutyryloxy-7-hydroxytropane, 3-tropoyloxy-6-isobutyryloxytropane, 3β-tropoyloxy-6β-isovaleroyloxytropane were tentatively identified. The alkaloids cyclotropine, dihydroaposcopolamine, 6,7-dehydrohyoscyamine and 4'-hydroxylittorine are reported for the first time for the genus Datura and 6,7-dehydrotropine for the family Solanaceae. Hyoscyamine and scopolamine figure as the major tropane alkaloids in the plant organs.


Adverse pregnancy outcome disclosure and women's social networks: a qualitative multi-country study with implications for improved reporting in surveys.
Globally, approximately 6,700 newborn deaths and 5,400 stillbirths occur daily. The true figure is likely higher, with under reporting of adverse pregnancy outcomes (APOs) noted. Decision-making in health is influenced by various factors, including one's social networks. We sought to understand APOs disclosure within social networks in Uganda, Ghana, Guinea-Bissau and Bangladesh and how this could improve formal reporting of APOs in surveys. METHODS: A qualitative, exploratory multi-country study was conducted within four health and demographic surveillance system sites. 16 focus group discussions were held with 147 women aged 15-49 years, who had participated in a recent household survey. Thematic analysis, with both deductive and inductive elements, using three pre-defined themes of Sender, Message and Receiver was done using NVivo software. Disclosure of APOs was a community concern, with news often shared with people around the bereaved for different reasons, including making sense of what happened and decision-making roles of receivers. Social networks responded with comfort, providing emotional, in-kind and financial support. Key decision makers included men, spiritual and traditional leaders. Non-disclosure was usually to avoid rumors in cases of induced abortions, or after a previous bad experience with health workers, who were frequently excluded from disclosure, except for instances where a woman sought advice on APOs. Communities must understand why they should report APOs and to whom. Efforts to improve APOs reporting could be guided by diffusion of innovation theory, for instance for community entry and sensitization before the survey, since it highlights how information can be disseminated through community role models. In this case, these gatekeepers we identified could promote reporting of APOs. The stage at which a person is in decision-making, what kind of adopter they are and their take on the benefits and other attributes of reporting are important. In moving beyond survey reporting to getting better routine data, the theory would be applicable too. Health workers should demonstrate a more comforting and supportive response to APOs as the social networks do, which could encourage more bereaved women to inform them and seek care.


Automated dynamic liquid-liquid-liquid microextraction followed by high-performance liquid chromatography-ultraviolet detection for the determination of phenoxy acid herbicides in environmental waters.
Automated dynamic liquid-liquid-liquid microextraction (D-LLLME) controlled by a programmable syringe pump and combined with HPLC-UV was investigated for the extraction and determination of 5 phenoxy acid herbicides in aqueous samples. In the extraction procedure, the acceptor phase was repeatedly withdrawn into and discharged from the hollow fiber by the syringe pump. The repetitive movement of acceptor phase into and out of the hollow fiber channel facilitated the transfer of analytes into donor phase, from the organic phase held in the pore of the fiber. Parameters such as the organic solvent, concentrations of the donor and acceptor phases, plunger movement pattern, speed of agitation and ionic strength of donor phase were evaluated. Good linearity of analytes was achieved in the range of 0.5-500 ng/ml with coefficients of determination, r2 > 0.9994. Good repeatabilities of extraction performance were obtained with relative standard deviations lower than 7.5%. The method provided up-to 490-fold enrichment within 13 min. In addition, the limits of detection (LODs) ranged from 0.1 to 0.4 ng/mL (S/N = 3). D-LLLME was successfully applied for the analysis of phenoxy acid herbicides from real environmental water samples.


The relationship between facial emotion recognition and executive functions in first-episode patients with schizophrenia and their siblings.
Although many studies have examined executive functions and facial emotion recognition in people with schizophrenia, few of them focused on the correlation between them. Furthermore, their relationship in the siblings of patients also remains unclear. The aim of the present study is to examine the correlation between executive functions and facial emotion recognition in patients with first-episode schizophrenia and their siblings. Thirty patients with first-episode schizophrenia, their twenty-six siblings, and thirty healthy controls were enrolled. They completed facial emotion recognition tasks using the Ekman Standard Faces Database, and executive functioning was measured by Wisconsin Card Sorting Test (WCST). Hierarchical regression analysis was applied to assess the correlation between executive functions and facial emotion recognition. Our study found that in siblings, the accuracy in recognizing low degree 'disgust' emotion was negatively correlated with the total correct rate in WCST (r = -0.614, p = 0.023), but was positively correlated with the total error in WCST (r = 0.623, p = 0.020); the accuracy in recognizing 'neutral' emotion was positively correlated with the total error rate in WCST (r = 0.683, p = 0.014) while negatively correlated with the total correct rate in WCST (r = -0.677, p = 0.017). People with schizophrenia showed an impairment in facial emotion recognition when identifying moderate 'happy' facial emotion, the accuracy of which was significantly correlated with the number of completed categories of WCST (R(2) = 0.432, P < .05). There were no correlations between executive functions and facial emotion recognition in the healthy control group. Our study demonstrated that facial emotion recognition impairment correlated with executive function impairment in people with schizophrenia and their unaffected siblings but not in healthy controls.


Pectoralis minor tendon transfer for irreparable anterosuperior cuff tears.
Tears of the subscapularis tendon are a frequent cause of shoulder dysfunction. Tendon transfer techniques have been devised to treat irreparable tears. The objectives of this study were to explore the anatomic feasibility of using the pectoralis minor tendon as a graft for subscapularis tendon tears, the safety of the procedure, and the scope of this approach in improving shoulder function. We performed open pectoralis minor transfer in 27 patients (22 men; mean age, 60 years) with irreparable tears of the upper two-thirds of the subscapularis tendon, grade III fatty degeneration, and irreparable supraspinatus tears. Constant and Simple Shoulder Test scores and functional outcomes were evaluated at 3, 12, and 24 months. All patients were available for follow-up. The pectoralis minor tendon easily reached the subscapularis footprint. There were no cases of musculocutaneous nerve or brachial plexus injury or graft failure. Active forward flexion improved from 127° to 177°; external rotation with the arm at the side declined by 11°. The Simple Shoulder Test score improved by 5 points and the Constant score by 41 points, although the strength subscore did not rise significantly. This study showed that it is anatomically feasible to use the pectoralis minor tendon as a graft to treat upper subscapularis lesions; the procedure is safe in terms of brachial plexus and musculocutaneous nerve injury; and pectoralis minor transfer can improve shoulder function and provide pain relief in patients with Lafosse grade III subscapularis tears, likely through a tenodesis effect, even in the presence of irreparable supraspinatus tears.


Focal white matter disruptions along the cingulum tract explain cognitive decline in amnestic mild cognitive impairment (aMCI).
White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases. However, our understanding of how fine-grained changes in microstructural properties along white matter tracts are associated with memory and cognitive decline in normal aging and mild cognitive impairment remains elusive. We quantified tract profiles with a newer method that can reliably measure fine-grained changes in white matter properties along the tracts using advanced multi-shell diffusion magnetic resonance imaging in 25 patients with amnestic mild cognitive impairment (aMCI) and 23 matched healthy controls (HC). While the changes in tract profiles were parallel across aMCI and HC, we found a significant focal shift in the profile at specific locations along major tracts sub-serving memory in aMCI. Particularly, our findings depict white matter alterations at specific locations on the right cingulum cingulate, the right cingulum hippocampus and anterior corpus callosum (CC) in aMCI compared to HC. Notably, focal changes in white matter tract properties along the cingulum tract predicted memory and cognitive functioning in aMCI. The results suggest that white matter disruptions at specific locations of the cingulum bundle may be a hallmark for the early prediction of Alzheimer's disease and a predictor of cognitive decline in aMCI.


Pre-service teachers' use of ICT to collaborate to complete assessment tasks.
This research explored the use of ICT products by n = 123 pre-service teachers to complete collaborative assessments. Students responded to a questionnaire relating to the use, benefits and limitations, and what would better enable the use of ICT for collaborative assessment purposes. The ICT products favoured by students did not support some key elements necessary for online collaboration, through either student use or product functionality. Poor Internet access was a commonly cited limitation with the effect of reducing access to available ICT skills training. Suggestions for changes to course structure and content and further research are made.


Modelling the climate change impact of mitigation (RCP 2.6) and high emission (RCP 8.5) scenarios on maize yield and possible adaptation measures in different agroclimatic zones of Punjab, India.
A simulation study was performed for assessing climate change impact on maize under Representative Concentration Pathways (RCPs 2.6 and 8.5) for Punjab, India. The study area comprised five agroclimatic zones (AZs) including seven locations. The bias corrected temperature and rainfall data from four models (CSIRO-Mk-3-6-0, FIO-ESM, IPSL-CM5A-MR and Ensemble) were used as input in CERES-Maize model which was run with constant management practices for two Punjab maize hybrids (PMH 1 and PMH 2). The maize yield for upcoming 70 years (2025-2095) was simulated and its deviations from the baseline (2010-2021) yield were computed under optimized sowing (early-May to early-July) and current sowing (end-May to end-June) period. With current sowing dates, the maize yield declined under both RCP 2.6 and RCP 8.5 scenarios, respectively in all the AZs, that is, by 4-23% and 60-80% in AZ II, by 5-60% and 60-90% in AZ III, by 9-30% and 50-90% in AZ IV and by 13-40% and 30-90% in AZ V. Though yield decline was lesser under RCP 2.6 as compared to RCP 8.5, but still it indicates that adaptive strategy such as shifting of sowing dates may be helpful in stabilizing the maize yield. The results for iterative combinations of sowing period revealed that early June sowing in AZ II for both the hybrids, mid- to end-June (Ludhiana and Amritsar) and end-May to mid-June (Patiala) sowings for PMH 1 were able to nullify the negative impact of climate change. Maize cultivation in AZ IV and AZ V would not be a suitable venture for farmers of the region. © 2023 Society of Chemical Industry.


The 'scientific artworks' of Doctor Paul Richer.
This article examines the little-known sculptures of pathology created by Doctor Paul Richer (1849-1933) in the 1890s for the so-called Musée Charcot at the Hôpital de la Salpêtrière in Paris. Under the direction of Doctor Jean-Martin Charcot (1825-1893), one of the founders of modern neurology, Richer was the head of the hospital's museum of pathological anatomy, as well as the Salpêtrière's resident artist. His 'series of figural representations of the principal types of nervous pathology' included busts of patients suffering from labio-glosso-laryngeal paralysis and myopathy, as well as sculptures depicting patients with Parkinson's disease and juvenile hypothyroidism. These patient portraits were seen as objective, while also paradoxically providing an alternative to mechanical media, such as the photograph and the cast, by permitting the doctor's intervention in not only controlling and animating the sitter, but also emphasising the patient's symptoms. This was a new kind of medical specimen: the 'scientific artwork', as they were called by a contemporary. This phrase, far from being an oxymoron, indicates the purposive collapse of the objective ('scientific') and subjective ('artistic') binary in Richer's sculptures of pathology. Through a detailed examination of three of Richer's works, this article problematises the categories traditionally used to describe, analyse and understand medical imagery and complicates our understanding of the relationship between science and art at the end of the nineteenth century.


Fibrinogen-related protein, FGL2, of hamster cauda epididymal fluid: Purification, kinetic analysis of its prothrombinase activity, and its role in segregation of nonviable spermatozoa.
Although the epididymal environment promotes the maturation and survival of spermatozoa, not all spermatozoa remain viable during passage through the epididymis. Does the epididymis has a protective mechanism(s) to segregate the viable sperm from defective spermatozoa? Previously, we identified 260/280 kDa oligomers (termed eFGL-Epididymal Fibrinogen-Like oligomer) are composed of two disulfide-linked subunits: a 64 kDa polypeptide identified as fibrinogen-like protein-2 (FGL2) and a 33 kDa polypeptide identified as fibrinogen-like protein-1 (FGL1). Our morphological studies demonstrated that the eFGL, secreted from the principal cells of the cauda epididymis, is polymerized into a death cocoon-like complex (DCF), masking defective luminal spermatozoa but, not the viable sperm population. In the present study, we purified FGL2 from hamster cauda epididymal fluid toward homogeneity and its prothrombinase catalytic activity was examined. Time-course conversion studies revealed that all prothrombin was converted to thrombin by purified hamster FGL2. Our biochemical studies demonstrate that FGL2 is a lipid-activated serine protease and functions as a lectin by binding specific carbohydrate residues. Co-immunoprecipitation analysis demonstrated that FGL2 of cauda epididymal fluid is ubiquitinated but not the FGL1. We propose that FGL2/FGL1 oligomers represent a novel and unique mechanism to shield the viable sperm population from degenerating spermatozoa contained within the tubule lumen.


Does Minimally Invasive Mitral Valve Repair Mean Less Postoperative Pain?
Rapid recovery after minimally invasive mitral valve (MV) repair has been demonstrated in many studies, but the issue of postoperative pain has not been fully elucidated. We evaluated pain scores and medication use in patients undergoing MV repair by minimally invasive surgery (MIS) and open sternotomy (OS). Between 2008 and 2019, 1332 patients underwent isolated MV repair by OS, and 913 underwent minimally invasive MV repair. After 1:1 propensity score matching, the study included 709 patients in each group. Opioid use was quantified as oral morphine equivalents in milligrams for each hospital day. The highest pain scores were collected from a visual analogue scale at 6-hour intervals. Predictive modeling was employed to compare pain medications and pain scores between the groups. The postoperative median length of stay was 3 (3-4) and 5 (4-5) days for the MIS and OS groups, respectively (P < .001). The predicted geometric mean oral morphine equivalents demonstrated lower opioid use for the MIS group compared with the OS group for the first 4 days. However, the predicted mean pain score was higher in the first 24 hours for the MIS group compared with the OS group (4.7 [4.5-4.8] vs 4.4 [4.3-4.5], respectively, on a visual analogue scale of 0 to 10). MV repair by MIS methods was associated with decreased opioid use but not with decreased postoperative pain scores. Possible explanations include the difference in incision site pain and subjective differences in postoperative pain expectations.


Apathetic symptom presentations in patients with severe traumatic brain injury: Assessment, heterogeneity and relationships with psychosocial functioning and caregivers' burden.
Apathy is frequently described following traumatic brain injury (TBI) and defined on the basis of three dimensions (emotional blunting, lack of initiative, lack of interest), which are commonly assessed by the Apathy Inventory (AI). The aims were (1) to explore the psychometric properties of this scale in the TBI population and the relationships between the dimensions; and (2) to determine whether sub-groups of patients differing with respect to the three AI dimensions could be identified and to examine their differences on psychosocial functioning and caregivers' burden. Close relatives of 68 patients with severe TBI were given the AI and two questionnaires to assess their subjective burden and patients' changes in psychosocial functioning. The scores distribution and the sensitivity of each sub-scale showed that the AI can be used as a screening tool in the TBI population. Four clusters were identified: one group with high scores on each dimension, one group with low scores on each dimension, one group with high emotional blunting alone and another with elevated lack of initiative/interest. The high apathetic group and the lack of initiative/interest group were associated with poorer psychosocial functioning and the high apathetic group was related to subjective burden. These results shed new light on the concept of apathy in patients with TBI and underline the necessity to take into account the various profiles of symptoms of apathy.


Fatal injuries and alcohol.
We reviewed fatal injuries in Fulton County, Georgia, in collaboration with the medical examiner's office. This county encompasses most of the city of Atlanta and has a population of approximately 600,000 persons. Information collected for 1981 and 1982 was analyzed; and the results of blood alcohol content (BAC) testing and toxic screens were reviewed for all victims of homicide, suicide, and unintentional fatal injuries who died within six hours of being injured. Seventy-one percent of 271 homicide victims had been drinking, and 51 percent had BACs greater than or equal to 0.1 mg/dL. Of 153 suicide victims, 37 percent had been drinking and 20 percent had BACs greater than or equal to 0.1 mg/dL. Of 54 drivers who died in single-vehicle collisions, 78 percent had been drinking; 54 percent of 162 victims of nonvehicular unintentional fatal injuries had positive blood alcohol levels. There was little evidence of the use of psychotropic drugs among victims of fatal injury. Most of the victims of homicide and unintentional fatal injuries who had positive toxic screens also had a positive blood alcohol tests.


Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat.
A study has been made of the mechanism of the mutual antagonism between copper and zinc in rats. Dietary zinc concentrations of up to 450 mg/kg had no effect on intestinal 64Cu absorption but 900 mg/kg caused a 40% reduction. This was associated with an increase in the mucosal uptake of 64Cu in the small intestine. This occurred mainly in the form of metallothionein and it appeared that copper displaced zinc from the protein after its synthesis had been induced by zinc. Ths intestinal absorption of 65Zn was decreased by 20% when the dietary copper intake was increased from 3 to 24 mg/kg. Further increases in copper intake to 300 mg/kg did not cause any additional decrease in 65Zn absorption or any change in the association of intestinal 65Zn with metallothionein. Concentrations of this protein in the intestinal mucosa were not influenced by dietary copper intake.


Delayed C5 Palsy After Anterior Cervical Decompression Surgery: Preoperative Foraminal Stenosis and Postoperative Spinal Cord Shift Increase the Risk of Palsy.
Postoperative C5 palsy is a well-known complication after cervical decompression with either a posterior or an anterior approach. Its cause has been discussed more regarding the posterior approach. The main hypothesis is that postoperative spinal cord shift causes root traction and palsy. However, the pathogenesis in anterior cases has not been fully described. Therefore, the purpose of this study was to clarify the risk factors for C5 palsy in the anterior approach through our C5 palsy cases. A total of 149 surgical patients with an anterior cervical lesion were treated by a specific spinal surgeon under consistent same treatment strategy. Of these patients, 88 who satisfied the evaluation criteria were enrolled. Postoperative C5 palsy was defined as postoperative weakness of the deltoid with or without weakness of the biceps brachii. Risk factors of C5 palsy were extracted from clinical backgrounds, surgical approaches, and radiologic findings from patients with palsy. Four sides of 3 individuals (4.6%) who underwent multiple corpectomy developed C5 palsy. All paralyses became evident several days after the surgery and recovered. Older age, multiple corpectomy, postoperative spinal cord shift, and foraminal stenosis of C4-5 and C5-6 were statistically extracted as causative factor of C5 palsy. In the patients with palsy, distortion of the anterior nerve root as a result of a residual vertebral spur was observed with anterior spinal cord shift after anterior corpectomy. Multiple corpectomy for patients with longer anterior lesions and locally developed kyphosis is related to a larger postoperative cord shift, which can cause the occurrence of C5 palsy. Moreover, C4-5 or C5-6 foraminal stenosis can accelerate tethering of the C5 or C6 nerve root. Older patients undergoing multiple corpectomy are susceptible to these risks of palsy. Appropriate patient selection and sufficient additional foraminotomy should be considered for extensive anterior lesions and locally developed kyphosis to avoid postoperative C5 palsy.


Climate resilience of dry season cereals in India.
India is the world's second largest producer of wheat, with more than 40% increase in production since 2000. Increasing temperatures raise concerns about wheat's sensitivity to heat. Traditionally-grown sorghum is an alternative rabi (winter season) cereal, but area under sorghum production has declined more than 20% since 2000. We examine sensitivity of wheat and sorghum yields to historical temperature and compare water requirements in districts where both cereals are cultivated. Wheat yields are sensitive to increases in maximum daily temperature in multiple stages of the growing season, while sorghum does not display the same sensitivity. Crop water requirements (mm) are 1.4 times greater for wheat than sorghum, mainly due to extension of its growing season into summer. However, water footprints (m3 per ton) are approximately 15% less for wheat due to its higher yields. Sensitivity to future climate projections, without changes in management, suggests 5% decline in wheat yields and 12% increase in water footprints by 2040, compared with 4% increase in water footprint for sorghum. On balance, sorghum provides a climate-resilient alternative to wheat for expansion in rabi cereals. However, yields need to increase to make sorghum competitive for farmer profits and efficient use of land to provide nutrients.


The medial approach to triple arthrodesis. Indications and technique for management of rigid valgus deformities in high-risk patients.
Between 1995 and 2002 the authors treated 17 patients who had a rigid hindfoot valgus deformity, and for whom a triple arthrodesis was planned, using a single medial incision. The indication for surgery was pain that was refractory to shoe wear, orthotic, and brace modifications. The severity of the hindfoot deformity itself was not a sufficient indication for this procedure. All 17 patients were examined a mean of 3.5 years following surgery (1-8 years). Subtalar and talonavicular arthrodesis was achieved in all patients and calcaneocuboid arthrodesis was achieved in 15 of 17 patients (2 asymptomatic pseudoarthrosis). The medial approach to triple arthrodesis is a reliable procedure, and can be used with a predictable outcome in patients who are at risk for wound healing complications for correction of hindfoot valgus deformity.