Rehabilitation of hearing and communication functions in patients with NF2.
Most patients with neurofibromatosis type 2 (NF2) lose hearing either spontaneously or after removal of their neurofibromas. The patient may benefit from conventional hearing aids if, due to modern microsurgery and intraoperative monitoring the integrity of the cochlea and the 8th nerve is preserved. With lost auditory function but preserved electrical stimulibility of the 8th nerve a cochlear implant may be appropriate. But if the patients have no remaining 8th nerve to stimulate, there is no benefit from cochlear implants. Until some years ago, vibrotactile aids, lip-reading, and sign language have been the only communication modes available to these patients. With auditory brain stem implants it is now possible to bypass both the cochlea and the 8th nerve and to stimulate the cochlear nucleus directly. Stimulation of the devices produces useful auditory sensations in almost all patients. Testing of perceptual performance indicated significant benefit from the device for communication purposes, including sound-only sentence recognition scores and the ability to converse on the telephone. Also lip-reading is significantly improved with brain stem implants. The successful work of an auditory brainstem program center depends very much on the close interdisciplinary collaboration between the Departments of Neurosurgery and ENT-surgery. In the future new developments like speech processing strategies and new designed electrodes accessing the complex tonotopic organization of the cochlear nucleus may further improve rehabilitation in these patients who would have been deaf some years ago.


Pure natural orifice transluminal endoscopic surgery (NOTES) with ultrasonography-guided transgastric access and over-the-scope-clip closure: a porcine feasibility and survival study.
Most natural orifice transluminal endoscopic surgery (NOTES) procedures to date rely on the hybrid technique with simultaneous laparoscopic access to protect against access-related complications and to achieve adequate triangulation for dissection. This is done at the cost of the potential benefits of this new minimally invasive technique. This study aimed to evaluate the feasibility and safety of a transgastric (TG) pure-NOTES procedure in a diagnostic setting. A TG pure-NOTES procedure with endoscopic ultrasonograpy (EUS)-guided access and over-the-scope-clip (OTSC) closure was performed for 10 pigs in a survival and feasibility study. A full macroscopic necropsy with subsequent histologic evaluation was performed on postoperative day (POD) 14. The outcome parameters were uncomplicated follow-up assessment, survival, intraoperative complications, intraabdominal pathology, macroscopic full-thickness closure, and histology-proven full-thickness healing of the gastrotomy. An uncomplicated postoperative course was reported for 9 of the 10 pigs, and survival was reported for all 10 pigs. For all the pigs, EUS-guided access was performed successfully with a median duration of 25 min (range, 12-62 min) and without intraoperative complications or access-related lesions at necropsy. An OTSC closure was achieved with a median duration of 11 min (range, 3-28 min). The OTSC provided immediate closure, but according to the authors' definition of a full-thickness healing evaluated by histologic examination, this was not achieved in any of the cases. Although all the animals survived until POD 14, intraabdominal chronic abscesses were present in 3 of the 10 pigs at necropsy. The EUS-guided TG access proved to be feasible without access-related complications. Although OTSC provided an immediate closure, the histopathology raised concerns regarding the risk of perforation. Together with the high risk of intraabdominal infection, TG pure-NOTES is not yet ready for routine clinical practice.


The haemoglobin types of northern Nigerian sheep.
The haemoglobin type of 515 sheep from various areas in northern Nigeria was determined. The gene-frequency of the Hb-B type was 1.00 in Uda and Balamy sheep and 0.998 in Yankassas.


Postnatal development of rat pups is altered by prenatal methamphetamine exposure.
There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MA-exposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks after birth, while not affecting physical or sexual maturation.


Hierarchical three-dimensional branched hematite nanorod arrays with enhanced mid-visible light absorption for high-efficiency photoelectrochemical water splitting.
Herein, we presented hierarchical three-dimensional (3D) branched hematite nanorod arrays (NAs) on transparent fluorine-doped tin oxide (FTO) conductive glass substrates, which exhibited high PEC water splitting performance due to the enhancement of mid-visible light harvesting as well as charge separation and transfer. The introduction of a TiO2 underlayer made the as-prepared 3D branched hematite NAs achieve a photocurrent density of 0.61 mA cm(-2) at 1.23 V vs. reversible hydrogen electrode (RHE) without high-temperature activation.


Controlling Nipah virus encephalitis in Bangladesh: Policy options.
Nipah virus (NiV) encephalitis is endemic in Bangladesh, with yearly seasonal outbreaks occurring since 2003. NiV has a notable case fatality rate, 75-100 per cent depending on the strain. In Bangladesh, primary transmission to humans is believed to be because of consumption of bat-contaminated date palm sap (DPS). Both the disease and the virus have been investigated extensively, however efforts to implement preventive strategies have met social and cultural challenges. Here we present a variety of community approaches to control the spread of Nipah encephalitis, along with advantages and disadvantages of each. This information may be useful to health workers and policymakers in potential NiV outbreak areas in Southeast Asia.


Increase in vesicular hand eczema after house dust mite inhalation provocation: a double-blind, placebo-controlled, cross-over study.
It is unclear whether the respiratory tract is involved in eliciting or aggravating eczematous lesions in patients with vesicular hand eczema. Objectives. To investigate the effect of inhalation of house dust mite (HDM) on vesicular hand eczema. Eighteen patients with vesicular hand eczema and HDM allergy received inhalation challenges with four concentrations of HDM in a randomized, double-blind, placebo-controlled, cross-over study. Early asthmatic reactions and late asthmatic reactions were defined as a placebo-corrected fall of 15% or more from baseline of forced expiratory volume in 1 second. Hand eczema was scored according to the Dyshidrotic Eczema Area and Severity Index (DASI) at baseline, and 1, 6, 24 and 48 hr. The median DASI increased significantly as compared with baseline at 6 and 48 hr after HDM inhalation. This increase was significantly different between the provocations at 6 hr. The median vesicles score increased significantly from baseline at 24 and 48 hr. Patients with a placebo-corrected increase in the number of vesicles at 24 hr and 48 hr had significantly more often late asthmatic reactions than those without an increase in the number of vesicles. Patients with a placebo-corrected increase of the DASI score at 24 hours had as a group a higher mean total IgE level than those without an increase of the DASI score. Hand eczema increased significantly more after HDM provocation than after placebo provocation. An increase in the number of vesicles was preceded by late asthmatic reactions. The group patients with an increase of hand eczema tended to have a higher mean total IgE level.


Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies.
Several studies have demonstrated the biologic and therapeutic significance of estrogen and progesterone receptors (ER and PR) in breast carcinomas. The aim of the current study was to examine the presence of androgen receptors (AR) in breast carcinomas. Two hundred cases of breast carcinoma, consisting of 145 invasive and 55 noninvasive (ductal carcinoma in situ [DCIS]) lesions, were examined using a monoclonal antibody against AR on formalin-fixed, paraffin-embedded archival material. The results were analyzed for correlations with immunohistochemically determined ER, PR, and HER-2/neu expression. Eighty-seven of the 145 cases (60%) of invasive carcinoma and 45 of the 55 cases (82%) of DCIS were AR-positive according to internationally standardized guidelines. The vast majority of Grade 1 carcinomas were positive for AR (90% of invasive Grade 1 carcinomas and 95% of Grade 1 DCIS), whereas in Grade 3 invasive carcinomas and DCIS, positive immunoreactions for AR were observed in 46% and 76% of cases, respectively. Among the cases of Grade 3 carcinoma, 33 invasive carcinomas (39%) and 17 DCIS lesions (68%) were ER-negative but AR-positive. Among Grade 1 carcinomas (invasive and DCIS), not a single case was positive for HER-2/neu, but most cases were intensely positive for AR. In contrast, many invasive Grade 3 carcinomas exhibited agreement between AR status and HER-2/neu status (AR-positive and HER-2/neu-positive, 30.5%; AR-negative and HER-2/neu-negative, 42.5%). Androgen receptors are commonly expressed in DCIS and in invasive breast carcinoma. A significant number of poorly differentiated carcinomas are ER-negative and PR-negative but AR-positive. Immunohistochemical examination of AR would be desirable because it would provide additional information about steroid receptors in breast carcinomas.


Attachment of [35S]cysteine to the labile site of the third component of complement via the alternative pathway.
Agarose beads to which [35S]cysteine had been attached by a disulfide bond were incubated in serum under conditions which permitted complement fixation via the alternative pathway, then washed and treated with dithiothreitol to release the cysteine. The dithiothreitol eluate contained C3b fragments which had been labeled covalently by the radioactive cysteine. Labeling was postulated to involve the reaction of the amino group of the cysteine with the "labile site," an acylating group which is exposed when C3 is converted to C3b during the operation of the alternative complement-fixing pathway.


Myzorhynchus series of Anopheles mosquitoes as potential vectors of Plasmodium bubalis in Thailand.
Ungulate malaria parasites and their vectors are among the least studied when compared to other medically important species. As a result, a thorough understanding of ungulate malaria parasites, hosts, and mosquito vectors has been lacking, necessitating additional research efforts. This study aimed to identify the vector(s) of Plasmodium bubalis. A total of 187 female mosquitoes (133 Anopheles spp., 24 Culex spp., 24 Aedes spp., and 6 Mansonia spp. collected from a buffalo farm in Thailand where concurrently collected water buffalo samples were examined and we found only Anopheles spp. samples were P. bubalis positive. Molecular identification of anopheline mosquito species was conducted by sequencing of the PCR products targeting cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 2 (cox2), and internal transcribed spacer 2 (ITS2) markers. We observed 5 distinct groups of anopheline mosquitoes: Barbirostris, Hyrcanus, Ludlowae, Funestus, and Jamesii groups. The Barbirostris group (Anopheles wejchoochotei or Anopheles campestris) and the Hyrcanus group (Anopheles peditaeniatus) were positive for P. bubalis. Thus, for the first time, our study implicated these anopheline mosquito species as probable vectors of P. bubalis in Thailand.


Identification keys to the Anopheles mosquitoes of South America (Diptera: Culicidae). IV. Adult females.
Morphological identification of adult females of described species of the genus Anopheles Meigen, 1818 in South America is problematic, but necessary due to their differing roles in the transmission of human malaria. The increase in the number of species complexes uncovered by molecular taxonomy challenges accurate identification using morphology. In addition, the majority of newly discovered species have not been formally described and in some cases the identities of the nominotypical species of species complexes have not been resolved. Here, we provide an up-to-date key to identify Neotropical Anopheles species using female external morphology and employing traditionally used and new characters. Morphological characters of the females of South American species of the genus Anopheles were examined and employed to construct a species/group identification key. Photographs of key characters were obtained using a digital Canon Eos T3i, attached to a microscope. The program Helicon Focus was used to build single in-focus images by stacking multiple images of the same structure. A morphological identification key to the adult females of species of the genus Anopheles described in South America is presented. Definitions and illustrations of the key characters are provided to facilitate use of key. Identification of species of the genus Anopheles based on female morphology is challenging because some key characters can be variable and overlapping among species. In addition, the majority of key characters are linked to color and shape of scales, their distribution on the head, scutum, abdomen, maxillary palpi, labium and legs, and pattern of pale and dark scales on dorsal and ventral surfaces of the wing veins. Thus, it is understandable that a specimen needs to be in good condition to be accurately identified. Morphologically similar species, such as those of the Konderi, Oswaldoi, Nuneztovari, Benarrochi and Albitarsis Complexes, and the Triannulatus and Strodei Groups, among others, cannot be accurately identified using characters included in the key. Further investigation will be required to exploit morphological characteristics for identification of members of those complexes, with formal description of new species.


Built Environments and Frailty in Older Adults: The JAGES Longitudinal Study Using Mediation Analysis.
The purpose of this study was to investigate the association between subjective built environment and the onset of frailty in older adults living in the community. In addition, we examined whether daily walking time, depressive symptoms, and social support from neighbors and friends are mediating factors. This was a longitudinal study using prospective cohort data from the 2013 Japan Gerontological Evaluation Study. Participants included 38,829 older adults who were not frail recruited from 22 cities and towns. The dependent variable, frailty, was assessed using the Kihon checklist. The explanatory variables were 5 items for the subjective built environment. The mediating variables were walking time of at least 30 minutes per day, a Geriatric Depression Scale (GDS) score of at least 5 points, and social support from neighbors and friends. We performed a causal mediation analysis of mediating effects between each built environment and frailty onset. Furthermore, the proportion of mediation was estimated. After 3 years of follow-up, frailty emerged in 2232 adults (6.7%) in 2016. Access to parks and sidewalks, access to fresh food stores, houses or facilities where people feel free to drop in, and fascinating views, or buildings reduced the onset of frailty. Mediators significantly associated with the built environment and onset of frailty were access to parks and sidewalks (walking time: 5.9%, GDS: 22.9%, social support: 5.9%), access to fresh food stores (GDS: 31.9%, social support: 4.0%), hills and steps (GDS: 20.6%), houses or facilities where people feel free to drop in (walking time: 4.0%, GDS 28.0%, social support: 10.4%), and fascinating views, or buildings (walking time: 7.8%, GDS: 42.1%, social support: 12.0%). We found that walking time, depression, and social support were mediating factors in the relationship between built environment and the onset of frailty.


Effects of acute systemic and intra-cerebral stimulation of cannabinoid receptors on sensorimotor gating, locomotion and spatial memory in rats.
Cannabinoid CB(1) receptors in the brain are targets of both endocannabinoid signalling and the psychoactive compounds of the hemp plant. They mediate neuronal effects of their ligands in various corticolimbic and striatal circuits by presynaptic regulation of transmitter release. This study investigates acute systemic effects of the full CB(1) receptor agonist WIN 55,212-2 (WIN) on prepulse inhibition (PPI) of the acoustic startle response (ASR), locomotor activity and spatial memory retrieval in an eight-arm radial-maze task. Furthermore, we tested the effect of local intra-cerebral micro-infusions of WIN into the nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal (dHIP) and ventral (vHIP) hippocampus and medial prefrontal cortex (mPFC). Systemic WIN (1.2 mg/kg) reduced PPI without affecting ASR, had no effect on locomotion in the open field, but impaired retrieval of spatial memory. Infusions of 5 microg/0.3 microl WIN into either NAc (core or shell), dHIP or VTA did not affect PPI and locomotion immediately afterwards. However, PPI was significantly reduced after intra-mPFC and intra-vHIP infusion of WIN. Furthermore, WIN infusion into dHIP increased the number of reference memory errors in the maze, suggesting impairment of memory retrieval. Our data support the notion that CB(1) receptor stimulation impairs sensorimotor gating most likely by modulation of neurotransmitter release in mPFC and vHIP. The lack of effects of local WIN infusions in NAc and VTA might be due to low receptor abundance in these regions. Additionally, CB(1) receptor activation in dHIP impairs spatial memory retrieval. Taken together, cortico-hippocampal cannabinoid receptors play an essential role in the regulation of cognitive and behavioural processes.


Acute Effects of a Warm-Up Intervention on Pain, Productivity, Physical Capacities and Psychological Perceptions Among Vineyard Workers: a Cluster Randomized Trial.
Agriculture is one of the sectors that are the most concerned by musculoskeletal disorders (MSDs). Workplace physical activity programs are one of the most promising solutions to prevent adverse consequences of MSDs such as pain or impairment in physical capacities. The aims of this study were twofold: (1) to investigate the acute effect of a warm-up session on pain, work performance, physical capacities and psychosocial perceptions among vineyard workers; (2) to determine the most beneficial warm-up modality for vineyard workers. A cluster randomized study was implemented among 92 French vineyard workers. A 15 min single session of warm-up was implemented among four groups corresponding to four different conditions: (1) hybrid warm-up intervention (HWU); (2) dynamic warm-up intervention (DWU); (3) stretching warm-up intervention (SWU); (4) no warm-up intervention (CONTROL). DWU showed significant increased performance (p < 0.05), increased heart rate (p < 0.001), better readiness to work (p < 0.05) and lower workload (p < 0.05) than the CONTROL. HWU showed a better readiness to work (p < 0.01). SWU showed better work quality (p < 0.05). However, the three different warm-up protocols did significantly not differ from the CONTROL group in terms of perceived pain intensity, and physical capacities. The present findings confirm some beneficial acute effects on performance, heart rate and psychological perceptions of a single warm-up session performed before pruning. The DWU seems to be the most beneficial warm-up modality. NCT05425693. Registered 06/16/2022 in www. gov .


Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.
Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.


Scleroderma kidney disease: a therapeutic approach with nephrectomy and hemodialysis.
A 49 year old black female patient with progressive systemic sclerosis (scleroderma), multiple organ system involvement, uremia and malignant hypertension, was treated with maintenance hemodialysis and bilateral nephrectomy. Bilateral nephrectomy controlled refractory hypertension and appeared to alter the natural course of systemic sclerosis.


The effects on left ventricular performance of verapamil and metoprolol singly and together in exercise-induced angina pectoris.
Concurrent therapy with the calcium channel blocker, verapamil, and the beta-blocking group of compounds is usually felt to be clinically contraindicated due to the former's potent dromotropic and negative inotropic actions. The basis of this assumption was examined in a rest and exercise hemodynamic study of the effects of verapamil and the cardioselective beta-blocking drug, metoprolol, in 22 patients with stable angina pectoris and angiographically confirmed coronary artery disease. In a randomized study, 11 patients were assessed following intravenous verapamil (16 mg) alone, 11 following intravenous metoprolol (10 mg) alone, and all 22 were assessed on combination therapy. The plasma levels achieved at the time of each hemodynamic assessment were in the therapeutic range. At rest, verapamil alone significantly lowered systemic arterial pressure and vascular resistance; metoprolol alone lowered heart rate and increased systemic vascular resistance without change in systemic arterial pressure. Combination therapy reduced systemic arterial pressure and heart rate without change in cardiac output and systemic vascular resistance. During upright bicycle exercise, the changes were directionally similar. Depression of cardiac function (i.e., reduced cardiac output at increased pulmonary artery occluded pressure) occurred following metoprolol but not following verapamil; the addition of verapamil did not accentuate the depression of function induced by metoprolol. These results suggested that in patients with stable coronary artery disease, without manifest conduction system abnormality, the cardiac depressant actions of verapamil were countered by its vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)


TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination.
Bone metastasis is a principal cause of mortality in patients with prostate cancer (PCa). Increasing evidence indicates that high expression of stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE) significantly activates the calcium (Ca2+) signaling pathway and is involved in multiple steps of bone metastasis in PCa. However, the regulatory mechanism and target therapy of STIM1 is poorly defined. Liquid chromatography-mass spectrometry analysis was performed to identify tetraspanin 18 (TSPAN18) as a binding protein of STIM1. Co-IP assay was carried out to explore the mechanism by which TSPAN18 inhibits STIM1 degradation. The biological function of TSPAN18 in bone metastasis of PCa was further investigated in vitro and in vivo models. We identified that STIM1 directly interacted with TSPAN18, and TSPAN18 competitively inhibited E3 ligase tripartite motif containing 32 (TRIM32)-mediated STIM1 ubiquitination and degradation, leading to increasing STIM1 protein stability. Furthermore, TSPAN18 significantly stimulated Ca2+ influx in an STIM1-dependent manner, and then markedly accelerated PCa cells migration and invasion in vitro and bone metastasis in vivo. Clinically, overexpression of TSPAN18 was positively associated with STIM1 protein expression, bone metastasis and poor prognosis in PCa. Taken together, this work discovers a novel STIM1 regulative mechanism that TSPAN18 protects STIM1 from TRIM32-mediated ubiquitination, and enhances bone metastasis of PCa by activating the STIM1-Ca2+ signaling axis, suggesting that TSPAN18 may be an attractive therapeutic target for blocking bone metastasis in PCa.


Nrf2: Redox and Metabolic Regulator of Stem Cell State and Function.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is ubiquitously expressed in most eukaryotic cells and functions to induce a broad range of cellular defenses against exogenous and endogenous stresses, including oxidants, xenobiotics, and excessive nutrient/metabolite supply. Because the production and fate of stem cells are often modulated by cellular redox and metabolic homeostasis, important roles of Nrf2 have emerged in the regulation of stem cell quiescence, survival, self-renewal, proliferation, senescence, and differentiation. In a rapidly advancing field, this review summarizes Nrf2 signaling in the context of stem cell state and function and provides a rationale for Nrf2 as a therapeutic target in stem cell-based regenerative medicine.


Protective effects of apigenin against acrylonitrile-induced subchronic sperm injury in rats.
This study aimed to investigate the protective effects of apigenin (AP), a flavonoid found in plants, against acrylonitrile (ACN)-induced subchronic sperm and testes injury in rats. Male Sprague-Dawley rats were randomly divided into four groups: a control group (corn oil), an ACN group (ACN 50 mg kg-1), an ACN + AP1 group (ACN + AP 234 mg kg-1), and an ACN + AP2 group (ACN + AP 468 mg kg-1). The ACN + AP group received AP by gavage after treatment with 50 mg kg-1 ACN for 30 min, whereas the rats in the control group were given an equivalent volume of corn oil. The gavage was conducted 6 days per week for 12 weeks. The results showed that AP increased the sperm concentration, motility, and mitochondrial membrane potential (MMP) (P < 0.05), which were reduced by ACN. Conversely, reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly decreased by AP (P < 0.05). AP improved the damage of the ultrastructure of sperm caused by ACN. AP reduced the pathological injuries and spermatogenic cell apoptosis caused by ACN in rat testes. AP also increased glutathione peroxidase activity and decreased MDA content. In conclusion, AP reduces ACN-induced decreasing sperm quality by inhibition of inflammation and oxidative stress.


Are There Variations in Mortality From Diverticular Disease By Sex?
Previous data reveal that females account for a disproportionate majority of all patients diagnosed with diverticulitis. This study analyzed the variation in mortality from diverticular disease by sex. This was a nationwide retrospective cohort study. Data were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research national registry. All citizens of the United States who died from an underlying cause of death of diverticulitis between January 1999 and December 2016 were included. The primary outcome addressed was overall mortality rate of diverticulitis by sex. Secondary outcomes included pattern variances in demographics and secondary causes of death. During the study period, 55,096 patients (0.12%) died with an underlying cause of death of diverticulitis from a total of 44,915,066 deaths. Compared with other causes, females were disproportionally more likely to die from diverticulitis than males (0.17% females vs 0.08% males; p < 0.001). Age-adjusted incidence of death was higher for females compared with males. Female patients were less likely to die within the hospital compared with males (OR = 0.72 (95% CI, 0.69-0.75); p < 0.001). Conversely, female patients were more likely to die either at nursing homes or hospice facilities (OR = 1.64 (95% CI, 1.55-1.73); p < 0.001). In addition, females with an underlying cause of death of diverticulitis were less likely to have a surgical complication as their secondary cause of death (OR = 0.72 (95% CI, 0.66-0.78); p < 0.001) but more likely to have nonsurgical complications related to diverticulitis such as sepsis (OR = 1.04 (95% CI, 1.01-1.05); p < 0.03), nonsurgical GI disorders such as obstruction (OR = 1.16 (95% CI, 1.09-1.24); p < 0.001), or chronic pelvic fistulizing disease (OR = 1.43 (95% CI, 1.23-1.66); p < 0.001). The study was limited by a lack of more specific clinical data. Females have a higher incidence of diverticular disease mortality. Their deaths are more commonly secondary to nonsurgical infections, obstruction, or pelvic fistulae. Female patients represent a particularly vulnerable population that may benefit from more intensive diverticulitis evaluation. See Video Abstract at http://links.lww.com/DCR/B257. ¿EXISTEN VARIACIONES EN LA MORTALIDAD POR ENFERMEDAD DIVERTICULAR POR GÉNERO?: Los datos anteriores revelan que las mujeres representan una mayoría desproporcionada de todos los pacientes diagnosticados con diverticulitis.Este estudio analizó la variación en la mortalidad por enfermedad diverticular por género.Estudio de cohorte retrospectivo a nivel nacional.Los datos se obtuvieron del registro nacional WONDER del Centro de Control de Enfermedades.Se incluyeron todos los ciudadanos de los Estados Unidos que murieron por una causa subyacente de muerte (UCOD por sus siglas en inglés) de diverticulitis del 1 / 1999-12 / 2016.El resultado primario abordado fue la tasa de mortalidad general de la diverticulitis por género. Los resultados secundarios incluyeron variaciones de patrones en la demografía y causas secundarias de muerte.Falta de datos clínicos más específicos.Durante el período de estudio, 55.096 pacientes (0,12%) murieron con un UCOD de diverticulitis de un total de 44.915.066 muertes. En comparación con otras causas, las mujeres tenían una probabilidad desproporcionadamente mayor de morir de diverticulitis que los hombres (0.17% F vs. 0.08% M, p <0.001). La incidencia de muerte ajustada por edad fue mayor para las mujeres que para los hombres. Las pacientes femeninas tenían menos probabilidades de morir en el hospital en comparación con los hombres (OR 0.72, IC 0.69-0.75, p <0.001). Por el contrario, las pacientes femeninas tenían más probabilidades de morir en asilos de ancianos o en centros de cuidados paliativos (OR 1.64, IC 1.55-1.73, p <0.001). Además, las mujeres con una UCOD de diverticulitis tenían menos probabilidades de tener una complicación quirúrgica como causa secundaria de muerte (OR 0.72, CI 0.66-0.78, p <0.001) pero más probabilidades de tener complicaciones no quirúrgicas relacionadas con la diverticulitis, como sepsis (OR 1.04, CI 1.01-1.05, p <0.03), trastornos gastrointestinales no quirúrgicos como obstrucción (OR 1.16, CI 1.09-1.24, p <0.001), o enfermedad fistulizante pélvica crónica (OR 1.43, CI 1.23-1.66, p <0,001).Las mujeres tienen una mayor incidencia de mortalidad por enfermedad diverticular. Sus muertes son más comúnmente secundarias a infecciones no quirúrgicas, obstrucción o fístulas pélvicas. Las pacientes femeninas representan una población particularmente vulnerable que puede beneficiarse de una evaluación más intensiva de diverticulitis. Consulte Video Resumen en http://links.lww.com/DCR/B257.


Astrocytes protect cultured neurons from degeneration induced by anoxia.
Neurons grown in cultures of dissociated brain cells degenerate when exposed to anoxia and deprived of glucose. We have developed culture systems in which neurons can be grown in the presence or absence of astrocytes and have used them to study the influence of astrocytes on the neuronal degeneration induced by anoxia and glucopenia. Cultures were prepared from fetal rat forebrains. Mixed cultures contained neurons (identified by immunocytochemical staining of neuron-specific enolase, NSE) and about an equal number of non-neuronal cells (identified by glial fibrillary acid protein). Pure neuronal cultures were prepared by adding a cytostatic compound (cytosine arabinoside) to the medium. Treated cultures were exposed for 4 h to glucose-free medium and an atmosphere of 95% N2 and 5% CO2, whereas control cultures were left in the usual medium containing glucose and in an atmosphere composed of 95% air and 5% CO2. After an interval of 24 h, cultures were fixed, taken for NSE staining, and the number of surviving neurons was counted. Exposure to anoxia and glucopenia reduced the number of surviving neurons in pure neuronal cultures to 5-10% of control levels. In contrast, in mixed cultures 40-60% of the neurons survived these conditions. Anoxia without glucose deprivation reduced the number of surviving neurons in both types of cultures to the same extent as anoxia combined with glucopenia. Glucose deprivation alone was ineffective. The findings suggest a protective influence of astrocytes on neurons under anoxic conditions. gamma-D-Glutamylglycine protected neurons in both types of cultures from anoxia-induced degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)


Reversible dementia in systemic lupus erythematosus without antiphospholipid antibodies or cerebral infarction.
Dementia is a very rare neurological manifestation of systemic lupus erythematosus (SLE) and has a deep link with antiphospholipid antibodies (APL) and cerebral infarction in its development. However, nonvascular dementia irrelevant to APL or cerebral infarction has not been reported in patients with SLE until now. We describe a case of reversible dementia in an SLE patient without APL or cerebral infarction which was successfully treated with corticosteroid and cyclophosphamide. There are two significant points in this case. One is that humoral factors other than APL might be involved in the development of dementia. Secondly, reversible dementia without APL or cerebral infarction may respond more favorably to immunosuppressive therapy.


Objective breast tissue image classification using Quantitative Transmission ultrasound tomography.
Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images' features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.


Neuroleptic binding to muscarinic M2 receptors of normal human heart in vitro and comparison with binding to M1 and dopamine D2 receptors of brain.
We determined by radioligand binding the equilibrium dissociation constants (Kd's) for seventeen neuroleptics at muscarinic M2 receptors of human heart atrium and compared these data with our previous data for binding to muscarinic M1 and dopamine D2 receptors of human brain. At the M2 receptor, the most potent compound was thioridazine; the least, molindone. If selectivity is defined as Kd at one receptor less than or equal to 0.1 Kd at the other receptor, no compound was selective for the M2 subtype. Two compounds, clozapine and triflupromazine, were selective for the M1 subtype. Thus, few neuroleptics have the assumed preferred property of M1 over M2 subtype selectivity. Such a feature could reduce extrapyramidal side effects, while reducing the likelihood of certain cardiac side effects.


The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem cells.
Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.


PIFA-Mediated Dearomatizative Spirocyclization of Phenolic Biarylic Ketones via Oxidation and C-C Bond Cleavage.
The dearomatizing spirocyclization of phenolic biarylic ketones using PhI(OCOCF3)2 as oxidant is presented. The reaction affords various cyclohexadienones through C-C bond cleavage under mild conditions. Mechanistic investigations reveal that an exocyclic enol ether acts as the key intermediate in the transformation.


CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection.
The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true "tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.


A pH dependent delivery of mesalazine from polymer coated and drug-loaded SBA-16 systems.
SBA-16 silica was synthesized and modified by post-synthesis method with amino groups. Wet milling in acidic media was applied for loading of poorly soluble drug mesalazine (5-aminosalicylic acid — 5-ASA) in different drug/carrier ratios (1:1; 0.75:1; 0.5:1; 0.25:1). The parent and drug loaded mesoporous silicas were characterized by XRD, TEM,N2 physisorption, thermal analysis, FT-IR and solid state NMR spectroscopy. The drug loaded mesoporous systems were single-coated with Eudragit S or double-coated with Eudragit S and Eudragit RL. The polymer coating significantly modified the rate of mesalazine release fromS BA-16NH2 materials. Applying the double coating method makes possible the sustained delivery of the drug in the intestinal area avoiding the burst release in the gastric fluid. The functionalized, polymer coated mesoporous system could be considered an appropriate oral delivery system for mesalazine. In addition, reduction of mesalazine cytotoxicity on epithelial cells could be achieved by its loading into mesoporous silica particles.


The Force Required to Inject a Column of Filler Through Facial Arteries.
Injectable fillers have become an integral part of facial rejuvenation, but vascular occlusion is a dreaded complication of such injections. To determine the force required by the fingertip onto the plunger of the syringe to cause retrograde migration. In this cadaver study, twelve 2-cm arterial segments and 4 fillers were tested. Injection pressure required to force a column of filler for 1 cm was measured. Five oculoplastics specialists were subsequently recruited and asked to inject the filler at a typical injection pressure. The nonhyaluronic acid filler required significantly more pressure to cause propagation of the material compared with all other fillers (p < .01). None of the other fillers differed significantly from each other. Typical injection pressures generated by experienced injectors were significantly lower than that required to cause propagation of filler at the desired velocity and significantly lower than mean arterial pressure. Measured pressure required to cause filler propagation was well within the normal range of the finger strength that can be generated by humans. Typical injection pressures from fingertip to plunger are lower than required to cause propagation of filler intravascularly.


Development of marker-free transgenic Jatropha curcas producing curcin-deficient seeds through endosperm-specific RNAi-mediated gene silencing.
Jatropha curcas L. is a potential biofuel plant and its seed oil is suitable for biodiesel production. Despite this promising application, jatropha seeds contain two major toxic components, namely phorbol esters and curcins. These compounds would reduce commercial value of seed cake and raise safety and environment concerns on jatropha plantation and processing. Curcins are Type I ribosome inactivating proteins. Several curcin genes have been identified in the jatropha genome. Among which, the Curcin 1 (C1) gene is identified to be specifically expressed in endosperm, whereas the Curcin 2A (C2A) is mainly expressed in young leaves. A marker-free RNAi construct carrying a β-estradiol-regulated Cre/loxP system and a C1 promoter-driven RNAi cassette for C1 gene was made and used to generate marker-free transgenic RNAi plants to specifically silence the C1 gene in the endosperm of J. curcas. Plants of transgenic line L1, derived from T0-1, carry two copies of marker-free RNAi cassette, whereas plants of L35, derived from T0-35, harbored one copy of marker-free RNAi cassette and three copies of closely linked and yet truncated Hpt genes. The C1 protein content in endosperm of L1 and L35 seeds was greatly reduced or undetectable, while the C2A proteins in young leaves of T0-1 and T0-35 plants were unaffected. In addition, the C1 mRNA transcripts were undetectable in the endosperm of T3 seeds of L1 and L35. The results demonstrated that the expression of the C1 gene was specifically down-regulated or silenced by the double-stranded RNA-mediated RNA interference generated from the RNAi cassette. The C1 promoter-driven RNAi cassette for the C1 gene in transgenic plants was functional and heritable. Both C1 transcripts and C1 proteins were greatly down-regulated or silenced in the endosperm of transgenic J. curcas. The marker-free transgenic plants and curcin-deficient seeds developed in this study provided a solution for the toxicity of curcins in jatropha seeds and addressed the safety concerns of the marker genes in transgenic plants on the environments.


Moderate weight-lowering effect of octopamine treatment in obese Zucker rats.
Octopamine is proposed as a substitution product of synephrine by diverse drug industries that advertise new weight-lowering products or medicinal plants enriched in this biogenic amine. We have already reported that octopamine is able to activate in vitro lipolysis in rat adipocytes via beta3-adrenergic receptor activation, while it activates glucose uptake in human fat cells via its oxidation by amine oxidases. In this work, we tested whether a chronic challenge with octopamine could exert anti-obesity effects. A treatment consisting in daily i.p. administration of octopamine (81 micromol/kg) was compared on a four-week period with calorie restriction in the genetically obese Zucker rat. Octopamine treatment resulted in a 19% decrease in body weight gain, when compared to the 177 g gained by controls during the same period. The decrease in body weight gain was detectable only after three weeks of treatment and was apparently not due to a pronounced and sustainable anorectic effect of octopamine since: 1) cumulated food consumption was only reduced by 10%; 2) the experimental 18% reduction of food intake provoked a rapid decrease in body weight gain, significant in less than two weeks. The lipolytic responses to isoprenaline or octopamine and the stimulation of glucose transport by insulin or by the amine oxidase substrate tyramine were unmodified by the treatments. Noteworthy, the elevated plasma insulin of obese rats was lowered by octopamine. This study shows that octopamine can reduce body weight gain in obese rats, without apparent adverse effects, but with less efficacy than beta3-AR agonists.


Single and repeated immobilization stress differentially trigger induction and phosphorylation of several transcription factors and mitogen-activated protein kinases in the rat locus coeruleus.
The locus coeruleus (LC) is a critical stress-responsive location that mediates many of the responses to stress. We used immunoblotting and immunohistochemistry to investigate changes in induction and phosphorylation of several transcription factors and kinases in the LC that may mediate the stress-triggered induction of tyrosine hydroxylase (TH) transcription. Rats were exposed to single or repeated immobilization stress (IMO) for brief (5 min), intermediate (30 min) or sustained (2 h) duration. Single IMO elicited rapid induction of c-Fos and phosphorylation of cyclic AMP response element-binding protein (CREB) without changing the expression of early growth response (Egr)1, Fos-related antigen (Fra)-2 or phosphorylated activating transcription factor-2. Repeated IMO triggered increased phosphorylation and levels of CREB along with transient induction of c-Fos and increased Fra-2 expression. Several mitogen-activated protein kinases were activated by repeated IMO, shown by increased phosphorylation of p38, c-Jun N-terminal kinase (JNK)1/2/3 and extracellular signal-regulated kinase (ERK1/2). ERK1 was the major isoform expressed, and ERK2 the predominant isoform phosphorylated. Repeated IMO elicited hyperphosphorylation of ERK1/2 selectively in TH immunoreactive neurons, with substantial nuclear localization. These distinct alterations in transcriptional pathways following repeated compared with single stress may be involved in mediating long-lasting neuronal remodeling and are implicated in the mechanisms by which acute beneficial responses to stress are converted into prolonged adaptive or maladaptive responses.


Environmentally relevant concentrations of Triclosan cause transcriptomic and biomolecular alterations in the hatchlings of Labeo rohita.
Suppression (p ≤ 0.05) of antioxidative/detoxification (except GPx and CYP3a) and cytoskeletal (except DHPR) genes but induction of metabolic (except for AST and TRY) and heat shock (except HSP60) genes of Labeo rohita hatchlings after 14 days of exposure to environmentally relevant concentrations of Triclosan (0.0063, 0.0126, 0.0252 and 0.06 mg/L) was followed by an increase (p ≤ 0.05) for most of the genes after 10 days recovery period. After recovery, LDH, ALT, CK, CHY, PA, HSP47 and DHPR declined, while SOD, CAT, GST, GR, GPx, CYP1a, CYP3a, AST, AChE, TRY, HSP60, HSP70, HSc71, HSP90 MLP-3, α-tropomyosin, desmin b and lamin b1 increased over exposure. Peak area of biomolecules (except 3290-3296, 2924-2925 and 2852-2855 cm-1) declined (p ≤ 0.01) more after recovery [except for an increase (p ≤ 0.01) at 1398-1401 cm-1]. CYP3a, CK, HSP90, MLP-3 and secondary structure of amide A are the most sensitive markers for the environmentally relevant concentrations of Triclosan.


Complete caudate lobectomy: its definition, indications, and surgical approaches.
There are three ways to approach and resect the caudate lobe of the liver, that is; and isolated caudate lobectomy, a combined resection of the liver overlying the caudate lobe, and a transhepatic anterior approach by splitting parenchyma of the liver. We had two patients with neoplasms originating in the caudate lobe who underwent a complete caudate lobectomy. Both patients have been doing well without liver dysfunction. Although after the transhepatic anterior approach we anticipated an adverse effect from splitting the parenchyma of the liver, the postoperative course was uneventful and similar to that of the right side approach.


Microvascular function in the peripheral vascular bed during ischaemia and oxygen-free perfusion.
To determine the influence of acute ischaemia and absence of leukocytes on the microvascular function and capillary permeability in skeletal muscle. Prospective, open study. University Department of Vascular Surgery and Institute of Medical Physiology. Ten isolated cat gastrocnemius muscles were perfused with oxygen-free Ringer-albumin solution through the femoral artery. At 5 microliters bolus with 14.8 MBq 51Cr-EDTA was injected through a side branch into the femoral artery, and the response function was detected over the muscle by a scintillation detector connected to a spectrometer and a computer. The perfusion coefficient was measured directly at the venous outlet. The response function was analysed in accordance with non-compartmental black box kinetic principles to give perfusion rate, capillary extraction fraction and capillary diffusional permeability-surface area product (PdS). In separate experiments the molecular size and the free diffusion coefficient of 51Cr-EDTA in water at 37 degrees C were determined by a modified true transient diffusion method. During perfusion the PdS-product increased as a function of flow rate, f, in accordance with the linear regression line PdS = 1.78 + 0.15 f between 5 to 60 ml/100 g/min. This permeative conductance was identical to that found previously in a similar experimental set up with oxygenated whole blood perfusion. During oxygen free perfusion the perfusion rate was a linear function of arterial perfusion pressure, and autoregulation of blood flow did not occur in response to variations of arterial perfusion pressures. The free diffusion coefficient in water at 37 degrees C for 51Cr-EDTA was 7.4 x 10(-6) cm2/s (n = 36), which corresponds to a Stokes-Einstein molecular radius, rSE, of 0.439 nm. In spite of complete anoxia and absence of normal microcirculatory flow regulating mechanisms there is no sign of changes in capillary diffusional permeability for smaller hydrophilic molecules and functional membrane damage is not elicited in the absence of oxygen under these conditions.


Sex Differences in Differentiated Thyroid Cancer.
Background: Sex dimorphism strongly impacts tumor biology, with most cancers having a male predominance. Uniquely, thyroid cancer (TC) is the only nonreproductive cancer with striking female predominance with three- to four-fold higher incidence among females, although males generally have more aggressive disease. The molecular basis for this observation is not known, and current approaches in treatment and surveillance are not sex specific. Summary: Although TC has overall good prognosis, 6-20% of patients develop regional or distant metastasis, one third of whom are not responsive to conventional treatment approaches and suffer a 10-year survival rate of only 10%. More efficacious treatment strategies are needed for these aggressive TCs, as tyrosine kinase inhibitors and immunotherapy have major toxicities without demonstrable overall survival benefit. Emerging evidence indicates a role of sex hormones, genetics, and the immune system in modulation of both risk for TC and its progression in a sex-specific manner. Conclusion: Greater understanding of the molecular mechanisms underlying sex differences in TC pathogenesis could provide insights into the development of sex-specific, targeted, and effective strategies for prevention, diagnosis, and management. This review summarizes emerging evidence for the importance of sex in the pathogenesis, progression, and response to treatment in differentiated TC with emphasis on the role of sex hormones, genetics, and the immune system.


Understanding tumour endothelial cell heterogeneity and function from single-cell omics.
Anti-angiogenic therapies (AATs) are used to treat different types of cancers. However, their success is limited owing to insufficient efficacy and resistance. Recently, single-cell omics studies of tumour endothelial cells (TECs) have provided new mechanistic insight. Here, we overview the heterogeneity of human TECs of all tumour types studied to date, at the single-cell level. Notably, most human tumour types contain varying numbers but only a small population of angiogenic TECs, the presumed targets of AATs, possibly contributing to the limited efficacy of and resistance to AATs. In general, TECs are heterogeneous within and across all tumour types, but comparing TEC phenotypes across tumours is currently challenging, owing to the lack of a uniform nomenclature for endothelial cells and consistent single-cell analysis protocols, urgently raising the need for a more consistent approach. Nonetheless, across most tumour types, universal TEC markers (ACKR1, PLVAP and IGFBP3) can be identified. Besides angiogenesis, biological processes such as immunomodulation and extracellular matrix organization are among the most commonly predicted enriched signatures of TECs across different tumour types. Although angiogenesis and extracellular matrix targets have been considered for AAT (without the hoped success), the immunomodulatory properties of TECs have not been fully considered as a novel anticancer therapeutic approach. Therefore, we also discuss progress, limitations, solutions and novel targets for AAT development.


Comparison of antimicrobial activity in the epidermal mucus extracts of fish.
The mucus layer on the surface of fish consists of several antimicrobial agents that provide a first line of defense against invading pathogens. To date, little is known about the antimicrobial properties of the mucus of Arctic char (Salvelinus alpinus), brook trout (S. fontinalis), koi carp (Cyprinus carpio sub sp. koi), striped bass (Morone saxatilis), haddock (Melanogrammus aeglefinus) and hagfish (Myxine glutinosa). The epidermal mucus samples from these fish were extracted with acidic, organic and aqueous solvents to identify potential antimicrobial agents including basic peptides, secondary metabolites, aqueous and acid soluble compounds. Initial screening of the mucus extracts against a susceptible strain of Salmonella enterica C610, showed a significant variation in antimicrobial activity among the fish species examined. The acidic mucus extracts of brook trout, haddock and hagfish exhibited bactericidal activity. The organic mucus extracts of brook trout, striped bass and koi carp showed bacteriostatic activity. There was no detectable activity in the aqueous mucus extracts. Further investigations of the activity of the acidic mucus extracts of brook trout, haddock and hagfish showed that these fish species had specific activity for fish and human pathogens, demonstrating the role of fish mucus in antimicrobial protection. In comparison to brook trout and haddock, the minimum bactericidal concentrations of hagfish acidic mucus extracts were found to be approximately 1.5 to 3.0 times lower against fish pathogens and approximately 1.6 to 6.6 folds lower for human pathogens. This preliminary information suggests that the mucus from these fish species may be a source of novel antimicrobial agents for fish and human health related applications.


Analysis of allele-specific gene expression using a target-oriented tiling microarray assay.
Advances in molecular and computational biology in recent years have led to the development or the improvement of methods for analyzing global gene expression. In most of these efforts, it is assumed that alleles of different origins contribute equally to the transcript pool. However, accumulating evidence suggests that many genes are not equally expressed from the paternal and maternal chromosomes. In addition to imprinting, the phenomenon of imbalanced allelic expression is widespread in heterozygous individuals. To distinguish transcript pools derived from different alleles present in the same organism, a number of methods have been developed. Here, we describe an oligonucleotide tiling microarray-based assay for analyzing allele-specific gene expression. Specifically targeting single-nucleotide polymorphisms, this two-step assay offers a high-throughput and multiplex method for detecting and quantifying unequal allelic expression that is readily applicable to many experimental systems.


Comparison of rifampicin and moxifloxacin efficacy in an experimental model of animal brucellosis.
Brucellosis is an important health issue in many parts of the world and clinicians are still seeking for better treatment choices. The aim of this study was to investigate the efficacy of moxifloxacin in an experimental brucellosis model and to compare its activity with rifampicin. Wistar albino rats infected with Brucella abortus were then randomized into 3 groups, which received rifampicin, moxifloxacin, and tap water, respectively. After 21 days, they were sacrificed and spleen, liver and blood cultures were performed. Spleen and liver cultures of all the animals yielded B. abortus in the control group, while these rates were 20% and 20% in the rifampicin group and 50% and 40% in the moxifloxacin group, respectively. The blood culture positivity was 66% in the control group and 10% in the moxifloxacin group. Blood cultures were all negative in the rifampicin group. As a conclusion, moxifloxacin might be an alternative choice in the treatment of brucellosis.


Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption.
Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia. We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene-diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3.8-4.0 g plant stanol esters a day for 8 weeks. At baseline, high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR-BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1) in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses. These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG-CoA reductase, CETP, or apoE genotype.


Genome-Wide Association to Study the Host-Specificity Determinants of Xanthomonas perforans.
Xanthomonas perforans and X. euvesicatoria are the causal agents of bacterial spot disease of tomato and pepper, endemic to the Southeastern United States. Although very closely related, the two bacterial species differ in host specificity, where X. perforans is the dominant pathogen of tomato and X. euvesicatoria that of pepper. This is in part due to the activity of avirulence proteins that are secreted by X. perforans strains and elicit effector-triggered immunity in pepper leaves, thereby restricting pathogen growth. In recent years, the emergence of several pepper-pathogenic X. perforans lineages has revealed variability within the bacterial species to multiply and cause disease in pepper, even in the absence of avirulence gene activity. Here, we investigated the basal evolutionary processes underlying the host range of this species using multiple genome-wide association analyses. Surprisingly, we identified two novel gene candidates that were significantly associated with pepper-pathogenic X. perforans and X. euvesicatoria. Both candidates were predicted to be involved in the transport/acquisition of nutrients common to the plant cell wall or apoplast and included a TonB-dependent receptor, which was disrupted through independent mutations within the X. perforans lineage. The other included a symporter of protons/glutamate, gltP, enriched with pepper-associated mutations near the promoter and start codon of the gene. Functional analysis of these candidates revealed that only the TonB-dependent receptor had a minor effect on the symptom development and growth of X. perforans in pepper leaves, indicating that pathogenicity to this host might have evolved independently within the bacterial species and is likely a complex, multigenic trait.


Signaling pathway in nerve growth factor induced histamine release from rat mast cells.
We investigated a signal transduction pathway involved in NGF induced histamine secretion from mast cells. We compared this mechanism with the exocytosis induced by basic secretagogue compound 48/80. Isolated rat peritoneal mast cells were obtained from male Wistar rats. Histamine release was assayed spectrofluorometrically. We found that tyrosine kinase inhibitor genistein, phospholipase C (PLC) inhibitor U-73122, phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor wortmannin, protein kinase C (PKC) inhibitors, staurosporine and GF109203X, but not MAP kinase inhibitors, SB203580 and PD98059, reduce histamine secretion in NGF provoked mast cell degranulation. In compound 48/80 mediated degranulation, we confirmed only the involvement of tyrosine kinase and PLC, but not PI-3 kinase, PKC and MAP kinases. Our results indicate that release of histamine from mast cells after stimulation with NGF is regulated by tyrosine kinase, PLC, PI-3 kinase and PKC, but not by MAP kinases. This biochemical pathway differs from that provoked by compound 48/80.


[Health worker safety as an essential condition for patient safety].
The greatest asset of any health system is its professionals, and they must be cared for in order to take care. It is necessary to emphasize that they are key for the resilience of our health systems. This is particularly important in crisis times and especially important for primary health care.During the COVID-19 pandemic, working conditions have been the main common latent factor for patient safety incidents. Primary Care professionals have worked in unsafe working conditions, with lack of means of protection, great uncertainty, lack of scientific knowledge and rapidly changing work protocols for dealing with cases and contacts of COVID-19 infection, with a high care pressure, long working hours, suspension of vacations, and even changes in their jobs. All of this has contributed to their becoming, not only the first victims of the pandemic, but also the second victims of the adverse events that occurred during it.Therefore, in this article we analyze the main risks and damages suffered by professionals in Primary Care and provide keys to contribute to their protection in future similar situations.


[Navigated transcranial magnetic stimulation for preoperative mapping of the eloquent cortex].
Brain tumor surgery in functionally relevant areas is particularly challenging. Preoperative functional mapping with navigated transcranial magnetic stimulation (TMS) was introduced into the clinical routine in 2009 and since then has seen widespread adoption. Accuracy and consistency of TMS motor and language mapping and its clinical relevance. Analysis of published scientific papers and discussion of the findings. Positive (i.e. motor responses are elicited) and negative cortical points for TMS motor mapping can be used for treatment planning and intraoperative decision making. Language mapping points (disruption of language function) positive in TMS can support treatment planning but should be confirmed intraoperatively with direct electrical stimulation. Negative TMS language mapping (language functions are not disrupted) correlates well with the gold standard of intraoperative testing. Recent studies reported improved treatment outcome after preoperative TMS mapping. Patients suffering from brain tumors in eloquent locations should be counseled based on individual functional mapping data before surgery and TMS is a valid non-invasive methodology which can provide such functional mapping.


Histochemical and histomorphological evidence of the modulating role of 1-isothiocyanate-4-methyl sulfonyl butane on cisplatin-induced testicular-pituitary axis degeneration and cholesterol homeostasis in male Sprague-Dawley rats.
This study examine the histochemical and histomorphological effect of 1-isothiocyanato-4-methyl sulfonyl butane (SFN) on cisplatin (CP) induced testicular alteration and cholesterol homeostasis. Ninety adult-male Sprague-Dawley rats were randomized into nine groups of ten (n=10) rats each. Group A (control) received normal saline, group B received a single dose of 10mg/Kg body weight (bwt) CP (i.p.), group C received 50mg/Kg bwt of SFN, group D received 100mg/Kg bwt of SFN, group E received 10mg/Kg bwt CP and 50mg/Kg bwt of SFN, group F received 10mg/Kg bwt CP and 100mg/Kg bwt of SFN, group G received 10mg/Kg bwt CP and 50mg/Kg bwt vitamin C, group H received 50mg/Kg bwt of SFN and 10mg/Kg bwt CP, group I received 100mg/Kg bwt of SFN and 10mg/Kg bwt CP. The procedure lasted for 56 days. Testicular histomorphology and histochemistry, testicular testosterone, sperm parameters, total antioxidant status (TSA), total oxidant status (TOS), oxidative stress index (OSI), and serum lipid profile were examined. Cisplatin decrease intra-testicular testosterone, sperm quality, and expression of glycogen and increases testicular TOS and OSI, serum lipid profile, collagen, and disruption of germinal epithelium. However, the intervention of SFN reversed the effect of CP on testes' weight and volume, DSP, ESP, testosterone production, TAS, TOS, and OSI. Histoarchitectecture showing normal seminiferous tubules and even distribution of glycogen and collagen fibers. Treatment with SFN ameliorate CP-induced testicular toxicity by reversing the cytotoxic mechanisms of CP.


Alkaline lysis of mammalian cells for sedimentation analysis of nuclear DNA. Conformation of released DNA as monitored by physical, electron microscopic and enzymological techniques.
The degree of single strandedness of the DNA released from rat liver nuclei by various alkaline lysing solutions (including some with sodium dodecyl sulfate) was determined both before and after sedimentation in alkaline sucrose gradients employing electron microscopy, melting profiles, circular dichroism measurements, and digestibility by S1 nuclease. Regardless of the technique employed, the results obtained following alkaline sucrose gradient centrifugation of the DNA are consistent. The DNA was completely single stranded as judged by electron microscopy, circular dichroism spectra, and digestibility by S1 nuclease, an enzyme that specifically hydrolyzes single-stranded DNA. This was not true if the DNA was analyzed following alkaline lysis of the nuclei but before centrifugation. Under conditions which gave a complete transition to the single-stranded state, as judged by melting profiles and circular dichroism spectra, only 10-15% of the DNA was hydrolyzed by S1 nuclease. An increase in the susceptibility of the released DNA to S1 nuclease was observed with increases in the pH of the lysing solution. In order to release DNA which was single stranded as judged by both physical and enzymological techniques, the rat liver nuclei were lysed for 30 min with a 0.3 M NaOH lysing solution containing 0.5% dodecyl sulfate, 0.3 M NaCl and 0.03 M EDTA.


Competition for two resources.
Tadpoles of the tree frog, Hyla chrysoscelis, were raised at low and high levels of two independent, growth-limiting resources: solid food substrates and ingestible particles. The effect of resource level on intraspecific competition was measured as the relative importance of interference versus exploitative competitive mechanisms. The levels of both solid food substrates and particles affected the outcome of competition among the tadpoles, despite their independent effects on growth. Current models of competition generally allow only one resource to limit population growth. This result implies that more than one resource may influence the outcome of intraspecific competition.


NEONATAL SEPSIS.
Neonatal sepsis continues to be a major cause of morbidity and mortality in India. To aid the diagnosis several direct and indirect methods are available. Sepsis screen has resulted in decrease in indiscriminate use of antibiotics. C-reactive protein can be easily estimated and is a useful indicator for favourable outcome or complication. The bacterial flora causing sepsis has changed over the years. Antimicrobial chemotherapy should be based on the prevalent organisms in the neonatal ICU. Outcome can be improved by judicious use of newer antibiotics and exchange transfusion when indicated.


The poor quality of information about laparoscopy on the World Wide Web as indexed by popular search engines.
This study was undertaken to determine the quality of information on the Internet regarding laparoscopy. Four popular World Wide Web search engines were used with the key word "laparoscopy." Advertisements, patient- or physician-directed information, and controversial material were noted. A total of 14,030 Web pages were found, but only 104 were unique Web sites. The majority of the sites were duplicate pages, subpages within a main Web page, or dead links. Twenty-eight of the 104 pages had a medical product for sale, 26 were patient-directed, 23 were written by a physician or group of physicians, and six represented corporations. The remaining 21 were "miscellaneous." The 46 pages containing educational material were critically reviewed. At least one of the senior authors found that 32 of the pages contained controversial or misleading statements. All of the three senior authors (LKN, NAO, GAF) independently agreed that 17 of the 46 pages contained controversial information. The World Wide Web is not a reliable source for patient or physician information about laparoscopy. Authenticating medical information on the World Wide Web is a difficult task, and no government or surgical society has taken the lead in regulating what is presented as fact on the World Wide Web.


Indications and results of side-to-side isoperistaltic strictureplasty in Crohn's disease.
Strictureplasty has commonly been used for short stenotic tracts, but it has rarely been applied to stenoses longer than 10 cm. Michelassi proposed a side-to-side isoperistaltic strictureplasty for single or multiple strictures that affected long bowel tracts. The experience and results obtained to date with this type of strictureplasty are limited. We therefore decided to review the cases in which we performed this procedure. Thirty-one patients, aged 21 to 66 years, underwent this operation between August 1996 and October 2002. Indications for surgery included subocclusion in 22 patients, malnutrition in 9 patients, and fistula or abscess in 6 patients. Two side-to-side isoperistaltic strictureplasties have been performed in jejunum, 6 in jejunum-ileum, 16 in the proximal ileum, 1 in terminal ileum, and 6 in the ileo-cecal tract. The average length of side-to-side isoperistaltic strictureplasty as 32.1 cm (range, 10-54 cm). Sixteen patients also underwent concomitant bowel resection and 17 patients have received additional strictureplasty. There was no perioperative mortality, nor were there any postoperative complications requiring reoperation. In all patients intestinal occlusion and malnutrition were resolved. Decrease of activity indices was observed in 62.3 percent of patients within 6 months after surgery. At an average follow-up of 26.4 months, six patients required reoperation, but in only one of them did the recurrence involve a previous strictureplasty site. In that case the side-to-side isoperistaltic strictureplasty was soft and was without signs of inflammation or stenosis. Side-to-side isoperistaltic strictureplasty seems to provide a technical solution leading to improvement when long intestinal inflamed tract are treated. Longer follow-up and larger experience is needed to validate this observation.


The association of wildfire smoke with respiratory and cardiovascular emergency department visits in Colorado in 2012: a case crossover study.
In 2012, Colorado experienced one of its worst wildfire seasons of the past decade. The goal of this study was to investigate the relationship of local PM2.5 levels, modeled using the Weather Research and Forecasting Model with Chemistry, with emergency department visits and acute hospitalizations for respiratory and cardiovascular outcomes during the 2012 Colorado wildfires. Conditional logistic regression was used to assess the relationship between both continuous and categorical PM2.5 and emergency department visits during the wildfire period, from June 5(th) to July 6(th) 2012. For respiratory outcomes, we observed positive relationships between lag 0 PM2.5 and asthma/wheeze (1 h max OR 1.01, 95 % CI (1.00, 1.01) per 10 μg/m(3); 24 h mean OR 1.04 95 % CI (1.02, 1.06) per 5 μg/m(3)), and COPD (1 h max OR 1.01 95 % CI (1.00, 1.02) per 10 μg/m(3); 24 h mean OR 1.05 95 % CI (1.02, 1.08) per 5 μg/m(3)). These associations were also positive for 2-day and 3-day moving average lag periods. When PM2.5 was modeled as a categorical variable, bronchitis also showed elevated effect estimates over the referent groups for lag 0 24 h average concentration. Cardiovascular results were consistent with no association. We observed positive associations between PM2.5 from wildfire and respiratory diseases, supporting evidence from previous research that wildfire PM2.5 is an important source for adverse respiratory health outcomes.


Developmental toxicity evaluation of inhaled 2-ethoxyethanol acetate in Fischer 344 rats and New Zealand white rabbits.
Pregnant Fischer 344 rats and New Zealand white rabbits were exposed to 2-ethoxyethanol acetate (EEA; CAS No. 111-15-9) vapor by inhalation on Gestational Days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 50, 100, 200, or 300 ppm, 6 hr/day. The animals were terminated on Gestational Day 21 (rats) or 29 (rabbits) and fetuses were examined for external, visceral, and skeletal malformations and variations. In rabbits, exposure to 100-300 ppm resulted in maternal toxicity: decreased weight gain at 100-300 ppm, clinical signs at 200-300 ppm, alterations in hematology at 100-300 ppm, reduced gravid uterine weight at termination at 200-300 ppm, and elevated absolute liver weight at 300 ppm. Developmental toxicity was observed at 100-300 ppm: an increased incidence of totally resorbed litters at 200-300 ppm, an increase in nonviable fetuses at 300 ppm, and a decrease in viable implants (live fetuses) per litter at 200-300 ppm. The incidence of fetal malformations (external, visceral, and skeletal) was increased at 200-300 ppm. The incidence of total malformations was 100% at 300 ppm and significantly increased at 200 ppm. Reduced fetal ossification was observed at 100-300 ppm. In rats, exposure to 100-300 ppm also resulted in maternal toxicity: reduced weight gain and reduced food consumption at 200-300 ppm and elevated relative liver weight and alterations in hematology at 100-300 ppm. Absolute maternal liver weight was increased at all EEA exposure concentrations; relative liver weight was increased at 100-300 ppm. Developmental toxicity was observed at 100-300 ppm: increased nonviable implantations/litter (300 ppm), reduced fetal body weight/litter (200-300 ppm), and increased incidence of external (300 ppm), visceral, and skeletal (100-300 ppm) variations indicative of toxicity. The incidence of visceral, skeletal, and total malformations was increased at 200-300 ppm. In conclusion, in both species, inhalation exposure to EEA during organogenesis produced maternal toxicity at 100-300 ppm and developmental toxicity at 100-300 ppm, including teratogenicity at 200-300 ppm. At 50 ppm in both species, there was no evidence of maternal or developmental toxicity, including teratogenicity.


Exogenous surfactant therapy: newer developments.
There are numerous pulmonary conditions in which qualitative or quantitative anomalies of the surfactant system have been demonstrated. In premature newborns with immature lungs, a functional deficit in surfactant is the main physiopathologic mechanism of the neonatal respiratory distress syndrome (RDS). Since the landmark pilot study of Fujiwara, published more than 20 years ago, the efficacy of exogenous surfactant for the treatment of neonatal RDS has been established by numerous controlled studies and meta-analyses. Promising results have also been reported in infants suffering from other lung disorders in which endogenous surfactant function is compromised. Enlightened by a growing insight into both the structure and function of the different surfactant components, a new generation of synthetic surfactants has been developed. Various complementary approaches have confirmed the fundamental role of the two hydrophobic proteins, SP-B and SP-C, in the surfactant system, thus opening the way to the design of analogues, either by chemical synthesis or expression in a prokaryotic system. These peptide-containing synthetic surfactant preparations are presently undergoing clinical trials, and may eventually replace the animal-derived surfactants currently used for the treatment of RDS.


Changes in pineal indoleamine metabolism in vitamin A deficient rats.
Weanling, male rats were fed a vitamin A deficient (VAD) diet from 20 to 77 days of age. The circadian rhythms of the precursors and metabolites of pineal melatonin were measured along with the activity of N-acetyltransferase (NAT). Significant decreases in peak melatonin levels (0100 hours) and in nightime NAT activity (0100 and 0300 hours) were found in the pineals of the VAD rats. In contrast, the contents of serotonin, 5-hydroxytryptophan and 5-hydroxyindole acetic acid were only moderately affected by the deficiency. Daily administration of 25 micrograms melatonin from 20 to 74 days of age markedly reduced NAT activity in control and VAD rats. These data suggest that NAT activity is more sensitive to chronic VAD than any other parameters of melatonin metabolism.


Freestanding Ambulatory Surgery Centers and Patients Undergoing Outpatient Knee Arthroplasty.
In 2018, Medicare removed total knee arthroplasty from the list of inpatient-only procedures, resulting in a new pool of patients eligible for outpatient total knee arthroplasty. How this change was associated with the characteristics of patients undergoing outpatient knee arthroplasty at hospital-owned surgery centers (HOSCs) vs freestanding ambulatory surgery centers (FASCs) is unknown. To describe the characteristics of patients undergoing outpatient, elective total and partial knee arthroplasty in 2017 and 2018 and to compare the cohorts receiving treatment at FASCs and HOSCs. This observational retrospective cohort study included 5657 patients having elective, outpatient partial and total knee arthroplasty in the Florida and Wisconsin State Ambulatory Surgery Databases in 2017 and 2018. Prior admissions were identified in the State Inpatient Database. Statistical analysis was performed from March to June 2022. Characteristics of patients undergoing surgery at a FASC vs a HOSC in 2017 and 2018 were compared. A total of 5657 patients (mean [SD] age, 64.2 [9.9] years; 2907 women [51.4%]) were included in the study. Outpatient knee arthroplasties increased from 1910 in 2017 to 3747 in 2018 and were associated with an increase in total knee arthroplasties (474 in 2017 vs 2065 in 2018). The influx of patients undergoing outpatient knee arthroplasty was associated with an amplification of differences between the patients treated at FASCs and the patients treated at HOSCs. Patients with private payer insurance seen at FASCs increased from 63.4% in 2017 (550 of 867) to 72.7% in 2018 (1272 of 1749) (P < .001), while the percentage of patients with private payer insurance seen at HOSCs increased, but to a lesser extent (41.6% [427 of 1027] in 2017 vs 46.4% [625 of 1346] in 2018; P < .001). In 2017, the percentages of White patients seen at FASCs and HOSCs were similar (85.0% [737 of 867] vs 88.2% [906 of 1027], respectively); in 2018, the percentage of White patients seen at FASCs had increased and was significantly different from the percentage of White patients seen at HOSCs (90.6% [1585 of 1749] vs 87.9% [1183 of 1346]; P = .01). Both types of facilities saw an increase from 2017 to 2018 in the percentage of patients from communities of low social vulnerability, but this increase was greater for FASCs (FASCs: 6.7% [58 of 867] in 2017 vs 33.9% [593 of 1749] in 2018; HOSCs: 7.6% [78 of 1027] in 2017 vs 21.2% [285 of 1346] in 2018). Finally, while FASCs and HOSCs had cared for a similar portion of patients with prior admissions in 2017 (7.8% [68 of 867] vs 9.4% [97 of 1027], respectively; P = .25), in 2018, FASCs cared for fewer patients with prior admissions than HOSCs (4.0% [70 of 1749] vs 8.1% [109 of 1346]; P < .001). This study suggests that the increase in the number of patients undergoing outpatient knee arthroplasty in 2018 corresponded to FASCs treating a greater share of patients who were White, covered by private payer insurance, and healthier. These findings raise a concern that as more operations transition to the outpatient setting, variability in access to FASCs may increase, leaving hospital-owned centers to bear a greater share of the burden of caring for more vulnerable patients with more severe illness.


Synthesis of cyclic diborenes with unprecedented cis-configuration.
The first examples of cis-configured diborenes - and the first cyclic diborenes - are isolated by taking advantage of stabilisation by chelating diphosphine ligands. The diborenes are prepared by a convenient one-pot reductive procedure that circumvents the need for a pre-formed base-adduct of the boron-containing precursor.


The effect of adenoidectomy on occlusal development and nasal cavity volume in children with recurrent middle ear infection.
The aim of the study was to examine the effect of adenoidectomy on occlusal/dentoalveolar development and nasal cavity volume in children who underwent tympanostomy tube insertion with or without adenoidectomy due to recurrent episodes of middle ear infection. This prospective controlled study consisted of two randomly allocated treatment groups of children, younger than 2 years, who had underwent more than 3-5 events of middle ear infection during the last 6 months or 4-6 events during the last year. At the mean age of 17 months tympanostomy tube placement without adenoidectomy (Group I, n=63) tympanostomy tube placement with adenoidectomy (Group II, n=74) was performed. At the age of 5 years 41 children of the original Group I (14 females, 27 males, mean age 5.2 yrs, SD 0.17) and 59 children of the original Group II (17 females, 42 males, mean age 5.2 yrs, SD 0.18) participated in the re-examination, which included clinical orthodontic examination defining morphological and functional craniofacial status and occlusal bite index to measure upper dental arch dimensions. Acoustic rhinometry and anterior rhinomanometry was made by otorhinolaryngologist at the same day. No statistically significant differences were found between the groups in the frequencies of morphological or functional characteristics or upper dental arch measurements or in the minimal cross-sectional areas or inspiratory nasal airway resistance measurements. Combining adenoidectomy with tympanostomy tube insertion in the treatment of recurrent middle ear infection at an early age (under the age of 2 years) does not seem to make any difference in occlusal development in primary dentition at the age of 5 years as compared to tympanostomy tube insertion only. Since adenoid size was not evaluated, the findings do not allow interpretation that hypertrophic adenoids should not be removed in children with continuous mouth breathing or sleep disordered breathing.


Functional analysis of ABCG2 gene in pigment transport of Neocaridina denticulata sinensis.
Many strains of Neocaridina denticulata sinensis (cherry shrimp) possess vivid body colors.However, the molecular underpinnings of these various body colors are scarcely understood. To study the role of the ABCG2 gene in the pigmentation of cherry shrimp, four strains (red, yellow, blue, and wild strains) were sampled. The sequence and expression pattern of ABCG2in tissues and embryos were analyzed, and the distribution of ABCG2 was also explored via WFISH (whole mount flurescence in situ hybridization). And further, RNA interference (RNAi) was used to explore the role of ABCG2 in body color deposition. The results showed that the ABCG2 sequence contained the conserved motif of Walker A, Walker B, Q-loop, d-loop, and H-loop. In tissues, ABCG2 was highly expressed in the epidermis of the four strains. During development stages, it was first expressed at the cleavage stage, then decreased at the gastrula stage, with the lowest expression at the pre-nauplius stage. From the metanauplius stage, its expression level was significantly upregulated until it reached the highest level at the membrane-zoea stage. WFISH showed that ABCG2 was first expressed at the cleavage stage in all four strains, and its distribution was similar from the cleavage stage to the before-zoea stage. The strongest positive signals were observed at the membrane-zoea stage, which was consistent with the qPCR results. Moreover, at the membrane-zoea stage, the positive signals of the four strains were mainly distributed in the compound eye and appendages. RNAi knockdown of ABCG2 encumbered the development of compound eye pigment cells (CEPCs) and erythrophores. It had effects on the expressions of other genes related to body color. These results suggest that ABCG2 is involved in the development of compound eye and the proliferation of erythrophores. This study provides new ideas for the cultivation of novel body colors in cherry shrimp at the molecular level.


Geospatial assessment of oil spill pollution in the Niger Delta of Nigeria: An evidence-based evaluation of causes and potential remedies.
Based on the archival data on oil facilities, oil spill incidents, and environmental conditions, we researched the plausible causes of oil spill disasters in the Niger Delta of Nigeria between 2006 and 2019. The data were analyzed for geospatial and statistical patterns, using ArcGIS and R programming platforms, respectively. A fuzzy logic algorithm was employed to generate three oil spill disaster models (hazard, vulnerability, and risk). Ordinary Least Square algorithm was adopted to model the relationships between oil spill and two sets of predictor variables: oil facilities (oil well, flow station, and pipeline) and disaster models. We found that, during the 23 years, the Niger Delta experienced 7940 oil spill incidents, of which 67% occurred onshore. A total of 4,950, 501, 855 episodes were attributed to sabotage, corrosion, and equipment failure, with 87%, 62%, and 45% occurring onshore, respectively. Besides, 81% of the 5320 onshore oil spill cases were attributed to sabotage, while corrosion and equipment failure accounted for mere 6% and 7% of the incidents, respectively. The estimated average risk index (R = 0.20) shows that the risk of an oil spill disaster in the Niger Delta is low. Whereas, 5% of the region is characterized by a high risk of oil spill disaster. Furthermore, the regression model infers that the oil spillages exhibit a positive relationship with disaster models and oil facilities at α = 0.10. However, only 16% of the incidents were explained by disaster models, while the oil facilities account for 23% of the total cases, indicating the influence of other factors. To avert further socio-environmental damage in the Niger-Delta, oil theft and sabotage should be curbed, polluted areas are remediated, and an all-inclusive socio-economic development is prioritized.


Nonketotic hyperglycinemia: analyses of glycine cleavage system in typical and atypical cases.
The molecular nature of the glycine cleavage system was investigated in eight patients with typical (neonatal) and two patients with atypical (late onset) nonketotic hyperglycinemia (NKH). The overall activity of the glycine cleavage system was found to be decreased in all of the liver and brain tissue studied, but it was undetectable or extremely low in typical NKH, whereas there was some residual activity in atypical NKH. Six patients with typical NKH had a specific defect in the P protein, and one a defect in the T protein; the activity of the T protein was defective in one patient with atypical NKH.


Sustained attention and the experience of flow.
The state of flow-often referred to as being "in the zone"-is characterized by the experience of deep, effortless concentration on the activity one is engaged in. While much of the flow literature seems to imply a tight link between flow and attention processes, relatively little work has assessed this question empirically. In the present study, we explored how the experience of flow relates to behavioural performance on the Sustained Attention to Response Task (SART). Flow was indexed at the state level using thought-probes and at the trait level via questionnaires. The main finding was that those who experienced more state-level flow during the SART made fewer commission errors during the task, indicating that flow is linked to better sustained attention. Interestingly, the correlation between flow and sustained attention performance was found to increase in the second half of the task. While trait flow was not related to SART performance, it was found to be predictive of state flow during the task, such that those who tended to experience higher levels of flow in their everyday lives also experienced more flow during the experiment.


The Grb2 binding domain of mSos1 is not required for downstream signal transduction.
Cellular Ras proteins are activated primarily by specific guanine-nucleotide releasing factors such as the Son of Sevenless (Sos) proteins. This activation event is thought to occur in response to plasma membrane localization of a complex containing Sos and a small adapter protein Grb2. We have isolated a dominant mutant allele of mSos1 which transforms Rat1 cells, yet is no longer able to bind Grb2. Biochemical experiments reveal that the subcellular distribution of this truncated Sos protein is not altered with respect to the wild type Sos protein. These data argue against a role for Grb2 in the direct recruitment of Sos proteins to the plasma membrane and suggest that Grb2 may function to overcome negative regulation of Sos by its C terminus.


Bacterial, PCR and clinico-pathological diagnosis of naturally occurring pneumonic pasturellosis (mannheimiosis) during subtropical climate in sheep.
Mannheimia haemolytica is causative agent of pneumonic pasteurellosis (mannheimiosis) that causes huge economic losses to livestock farmers. We investigated the microbial and clinico-pathological patterns associated with ovine pneumonic pasturellosis during an outbreak. Prior to death, infected sheep revealed clinical signs including dyspnoea, salivation, pyrexia and mucopurulent nasal discharge. Mortality was significantly (p < 0.05) high in young sheep as compared to adults. Necropsy findings revealed presence of froth in trachea, congestion and consolidation of lungs, pulmonary edema, severe pleural adhesions, pericarditis, hemorrhages on mucosa of jejunum and kidneys. Histopathological examination revealed circumscribed and centrally calcified necrotic areas punctuated with chronic inflammatory cells and interstitial pneumonia. Moreover, bronchial epithelial hyperplasia, edema, congestion, mononuclear cell infiltration, thick interlobular septae and peri-vascular cuffing were the striking changes in lungs. Furthermore, lungs showed severe fibrin depositions along with abundant amount of fibrin meshwork on pleura infiltrated with chronic inflammatory cells. Histologically, liver, kidneys and lymph nodes showed degenerative changes. Mannheimia haemolytica and Pasteurella multocida were differentially identified on the basis of culture characteristics and biochemical tests. M. haemolytica was further confirmed by using polymerase chain reaction. From the findings of current study, it is concluded that M. haemolytica is a major respiratory threat in small ruminants that causes severe pneumonic changes in infected animals.


National-scale monitoring of historic used organochlorine pesticides (OCPs) and current used pesticides (CUPs) in Chinese surface soil: Old topic and new story.
Along with the restriction and prohibition of historic used organochlorine pesticides (OCPs), current used pesticides (CUPs) were widely used as alternatives. In order to investigate the pollution characteristics of pesticides, the levels and spatial distributions of OCPs and CUPs in 154 surface soil across China were comprehensively compared. Totally, 107 target pesticides were screened, and 20 OCPs and 34 CUPs were detected. The numbers of co-occurred pesticides in single soil sample were from 17 to 36 indicating the diversity and complexity of pesticides pollution. The concentrations of OCPs in urban soils were higher than rural soils, while rural > urban for CUPs. Furthermore, obviously different spatial distribution patterns were found for OCPs and CUPs. For OCPs, the secondary distribution pattern was dominant. For CUPs, the primary distribution pattern was obviously observed due to their current extensive usage. In addition, higher concentrations of both CUPs and OCPs were accumulated in the Northeast China Plain due to long-range atmospheric transport and deposition. Along with the old topic of OCPs, the study pointed out the preliminary understanding of CUPs pollution characteristic in surface soil of China, which provided a new story with the deep understanding of their environmental fate in both China and the world.


[Craniofacial growth. 1. Critical review of the most authoritative current knowledge].
After an analysis of the knowledge of today about the cranio-facial growth, the author presents a theory of the structural function as a proper conclusion of the change from a genetic hypothesis to a functional matrix. This theory will explain some skeletal modifications that before were incomprehensible.