Efficacy and safety of rituximab biosimilar (CT-P10) in IgG4-related disease: an observational prospective open-label cohort study.
Rituximab is increasingly used in IgG4-related disease (IgG4-RD) but high costs limit its wide off-label administration. European and US regulatory agencies have recently approved rituximab biosimilars for the treatment of different rheumatologic and hematological conditions. No data are available, yet, on the efficacy and safety of rituximab biosimilars for the treatment of IgG4-RD. Scope of the present work is to evaluate the efficacy and safety of the rituximab biosimilar CT-P10 (RTX-B) in patients with IgG4-RD. Patients with active IgG4-RD, naïve to rituximab or switched from the originator (RTX-O) to the biosimilar were treated with RTX-B and prospectively followed-up for 18 months. Safety and efficacy were assessed at six months. Relapse rate was assessed at 18 months. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). Thirty-eight patients were included in this study. Thirty-three patients (87%) were naïve to RTX. Five patients (13%) relapsed after RTX-O and were switched to RTX-B. After six months, 21 patients (60%) achieved disease remission. The median serum IgG4 concentration decreased from 1344 to 575 mg/L (p < 0.01), and the median IgG4-RD RI decreased from 7.5 to 0 (p < 0.01). B-cell depletion was observed in all patients. Eight patients (36%) relapsed within 18 months. Side effects related to RTX-B administration were observed in 14 patients (37%). These results are in line with our previous experience with RTX-O. The (TruximaTM) rituximab biosimilar CT-P10 represents a safe and effective alternative to rituximab originator for the treatment of IgG4-RD.


Longitudinal association of midlife vision impairment and depressive symptoms: the study of Women's Health Across the Nation, Michigan site.
Poor vision affects physical health but the relationship with depressive symptoms among midlife adults (40-65 y), who often present with early stage vision impairment (VI), is not well understood. The goal of this study was to assess the impact of vision on depressive symptoms during midlife. The Michigan site of the Study of Women's Health Across the Nation conducted assessments of distance visual acuity at six consecutive, near-annual follow-up visits. At each visit, depressive symptoms (Center for Epidemiological Studies-Depression Scale) were assessed. VI was defined as mild (20/30-20/60) or moderate-severe (20/70 or worse). Multivariable logistic regression models using generalized estimating equations were used to assess the association of VI and reporting of depressive symptoms at the subsequent visit. At analytic baseline, the mean age of participants (N = 226) was 50.0 years (standard deviation = 2.6). More than half (53.5%) of women had mild VI and 8.0% had moderate-severe VI. Adjusting for age, preexisting depressive symptoms, race, education, economic strain, body mass index, and smoking, participants with mild and moderate-severe VI had 68% (95% C (0.97-2.90)) and 2.55-fold (95% CI 1.13-5.75) higher odds of reporting depressive symptoms at their subsequent study visit as compared with women without VI. Further adjustment for diabetes, hypertension, and osteoarthritis attenuated the estimates and the associations were no longer statistically significant. VI was associated with increased odds of future depressive symptoms among mid-life women. Timely detection and appropriate correction of VI may be important to consider in maintaining the mental health status of midlife women.


Photoactivated In Situ Generation of Near Infrared Cyanines for Spatiotemporally Controlled Fluorescence Imaging in Living Cells.
Photoactivated trimerization of 2,3,3-trimethyl-3H-indole derivatives created near infrared fluorophore Cy5. The synthetic method is air-tolerant, photosensitizer free, metal free, and condensation agent free. Living cells make Cy5 on a time scale of minutes under white light irradiation at a low power intensity, with the monomer as the only exogenous agent. The new method is promising to find applications in cell studies for in situ spatiotemporally controlled fluorescence imaging in living cells.


Prevalence of Airflow Obstruction in U.S. Adults Aged 40-79 Years: NHANES Data 1988-1994 and 2007-2010.
The study evaluated the change in the prevalence of airflow obstruction in the U.S. population 40-79 years of age from years 1988-1994 to 2007-2010. Spirometry data from two representative samples of the U.S. population, the National Health and Nutrition Examination Surveys (NHANES) conducted in 1988-1994 and 2007-2010, were used. The American Thoracic Society/European Respiratory Society (ATS/ERS) criteria were used to define airflow obstruction. Based on ATS/ERS criteria, the overall age-adjusted prevalence of airflow obstruction among adults aged 40-79 years decreased from 16.6% to 14.5% (p < 0.05). Significant decreases were observed for the older age category 60-69 years (20.2% vs. 15.4%; p < 0.01), for males (19.0% vs. 15.4%; p < 0.01), and for Mexican American adults (12.7% vs. 8.4%; p < 0.001). The prevalence of moderate and more severe airflow obstruction decreased also (6.4% vs. 4.4%; p < 0.01). Based on ATS/ERS criteria, during 2007-2010, an estimated 18.3 million U.S. adults 40-79 years had airflow obstruction, 5.6 million had moderate or severe airflow obstruction and 1.4 million had severe airflow obstruction. The overall age-adjusted prevalence of airflow obstruction among U.S. adults aged 40-79 years decreased from 1988-1994 to 2007-2010, especially among older adults, Mexican Americans, and males.


Immunoswitch Nanomodulators Enable Active Targeting and Selective Proliferation of Regulatory T Cells for Multiple Sclerosis Therapy.
Interleukin-2 (IL-2) used in multiple sclerosis (MS) therapy modulates the balance between regulatory T (Treg) cells and effector T (Teff) cells. However, the off-target activation of Teff cells by IL-2 limits its clinical application. Therefore, a rapidly prepared immunoswitch nanomodulator termed aT-IL2C NPs was developed, which specifically recognized Treg cells with high TIGIT expression thanks to the presence of an anti-TIGIT and an IL-2/JES6-1 complex (IL2C) being delivered to Treg cells but not to Teff cells with low TIGIT expression. Then, IL2C released IL-2 due to the specific expression of the high-affinity IL-2 receptor on Treg cells, thus enabling the active targeting and selective proliferation of Treg cells. Moreover, the anti-TIGIT of aT-IL2C NPs selectively inhibited the proliferation of Teff cells while leaving the proliferation of Treg cells unaffected. In addition, since the IL-2 receptor on Teff cells had medium-affinity, the IL2C hardly released IL-2 to Teff cells, thus enabling the inhibition of Teff cell proliferation. The treatment of experimental autoimmune encephalomyelitis (EAE) mice with aT-IL2C NPs ameliorated the severity of the EAE and restored white matter integrity. Collectively, this work described a potential promising agent for effective MS therapy.


Effects of the crossed acoustic reflex on distortion-product otoacoustic emissions in awake rabbits.
Recent studies in anesthetized cats suggest that contralateral-sound stimulation acts to suppress ipsilateral neural responses via the medial olivocochlear-efferent system. Activation of this descending efferent pathway presumably influences ipsilateral outer hair cell motility and, thus, cochlear micromechanics, resulting in reduced input to auditory-nerve fibers. The principal aim of the present study was to determine if contralateral-sound stimuli influence the generation of ipsilateral distortion-product otoacoustic emissions, in the ears of awake rabbits. The results showed no effects of contralateral stimuli on these emissions that could not be attributed to the crossed acoustic middle-ear reflex. The findings further indicate that distortion-product otoacoustic emission amplitudes over a wide range of frequencies can be dramatically reduced when the middle-ear reflex is activated.


A unique mode of keratinocyte death requires intracellular acidification.
The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca2+- and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged (∼60 min) Ca2+ elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca2+ elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis.


Increased Glucocorticoid Receptor Alpha Expression and Signaling in Critically Ill Coronavirus Disease 2019 Patients.
Critical illness is characterized by increased serum cortisol concentrations and bioavailability resulting from the activation of the hypothalamic-pituitary-adrenal axis, which constitutes an essential part of the stress response. The actions of glucocorticoids are mediated by a ubiquitous intracellular receptor protein, the glucocorticoid receptor. So far, data on coronavirus disease 2019 and glucocorticoid receptor alpha expression are lacking. Prospective observational study. One academic multidisciplinary ICU. Twenty-six adult coronavirus disease 2019 patients; 33 adult noncoronavirus disease 2019 patients, matched for age, sex, and disease severity, constituted the control group. All patients were steroid-free. None. Glucocorticoid receptor alpha, glucocorticoid-inducible leucine zipper expression, and serum cortisol were measured on ICU admission. In coronavirus disease 2019 patients, glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper messenger RNA expression were upregulated (4.7-fold, p < 0.01 and 14-fold, p < 0.0001, respectively), and cortisol was higher (20.3 vs 14.3 μg/dL, p < 0.01) compared with the control group. ICU coronavirus disease 2019 patients showed upregulated glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper expression, along with cortisol levels, compared with ICU noncoronavirus disease 2019 patients. Thus, on ICU admission, critical coronavirus disease 2019 appears to be associated with hypercortisolemia, and increased synthesis of glucocorticoid receptor alpha and induced proteins.


Inhibitory effect of a caerulein-like peptide on human gastric secretion.
A synthetic heptapeptide corresponding to the C-terminal heptapeptide of caerulein but characterized by a nor-leucyl residue replacing the methyonyl residue of caerulein, when given by i.v. infusion (2 mug/kg/h), inhibited by 70-80% pentagastrin (4 mug/kg/h)-stimulated gastric secretion...


Non-recovery animal model of severe facial paralysis induced by freezing the facial canal.
Some cases of peripheral facial paralysis are resistant to treatment, thus, a non-recovery model of facial paralysis is needed to develop new treatment strategies for this condition. The purpose of the current study was to develop an animal model of which facial palsy was severe and prolonged. Ten 8-week-old female Hartley guinea pigs weighing between 400 and 500 g were used for the animal model. The vertical segment of the facial canal was accessed via the otic bulla, without removing the bony wall of the facial canal. The canal was then frozen for 5 s using freeze spray. Facial movements, electroneurography (ENoG), histology, and changes in temperature were evaluated. All animals exhibited complete facial paralysis immediately after the procedure and recovered gradually, however, not all of them had recovered completely 15 weeks after freezing. The ENoG values one week after freezing for all animals (10/10) were 0%. Histological examination one week after freezing revealed that most of the vertically placed myelinated nerve fibers which had been frozen were remarkably affected and denatured. The number of vertically placed myelinated nerve fibers increased 15 weeks after freezing, but the nerve fibers were smaller than normal nerve fibers and were distorted in shape. Complete facial paralysis was induced in Hartley guinea pigs by freezing the facial canal. The behavioral, ENoG, and histopathological data suggest that the facial paralysis was severe and prolonged. This model may assist in developing novel treatment for severe facial palsy and facilitate basic research on facial nerve regeneration.


Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.
Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.


Measurement of lipid forces by X-ray diffraction and osmotic stress.
Lipid suspensions in aqueous solutions most often form multilamellar vesicles of uniformly spaced bilayers. Interlamellar spacing is determined by the balance of attractive van der Waals (charge fluctuation) and repulsive forces. This balance of forces, as well as membrane elasticity, can be probed by applied osmotic stress. We describe how osmotic stress can be imposed on multilamellar lipid samples to study lipid interactions.


Do sperm contribute to the buffering capacity of steelhead trout (Oncorhynchus mykiss) semen?
The motility of salmonid sperm is pH-sensitive and the buffering capacity of the seminal plasma is low. The objective of the present study was to determine the extent to which sperm contribute to the buffering capacity of whole steelhead (Oncorhynchus mykiss) semen. To determine the buffering capacity, semen and seminal plasma samples were titrated with HCl and pH measurements taken at 1-2 min. The buffering capacity of semen was not different from that of seminal plasma over the pH range 7.5 to 8.5 and was approximately 15% to 20% less over the range 6.0 to 7.0. Comparable results were obtained for the semen and seminal plasma of the chinook salmon (Oncorhynchus tshawytscha). To assess whether the intracellular environment could influence the buffering capacity, the effects of cell disruption with n-butanol and Triton X-100 (TX-100) were determined. Over the pH range 7.5 to 8.5, the presence of n-butanol or TX-100 resulted in a doubling of the buffering capacity of the semen; TX-100, but not n-butanol, increased semen buffering capacity over the pH range 6.0 to 7.0. To determine whether the sperm's intracellular compartment might contribute to the buffering capacity over a longer duration, semen and seminal plasma samples were acidified with HCl and the pH measured over several hours. These data suggest that intact sperm contribute no more than about 25% to the buffering capacity of whole semen. The buffering capacity of steelhead semen and seminal plasma were comparably and modestly temperature sensitive. The results suggest that the sperm may contribute to the buffering capacity of the semen over a physiological pH range, however, if so, the effect is relatively small.


A computer method for determining plaque size and plaque morphology.
We describe a computer method for determining plaque size and morphology from photographs of hemolytic plaques. The method eliminates any inter-measurer and intra-measurer inconsistencies that may arise when manual measurements are made on plaques whose boundaries are poorly defined. For circular plaques inner and outer plaque radii are determined. In addition the computer generates a density profile for each plaque, i.e., a plot of the film density versus the radial distance from the antibody forming cell. We demonstrate the use of the method by analyzing a time study of the growth of a single plaque.


Cytokine expression in trichloroethylene-induced hypersensitivity dermatitis: an in vivo and in vitro study.
The purpose of this study was to address the association between cytokine expression and the hypersensitivity dermatitis induced by trichloroethylene (TCE) exposure. 28 TCE-induced hypersensitivity dermatitis patients, 22 TCE exposed workers and 22 non-exposed controls were enrolled in the study. The serum levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α were analyzed using a magnetic colorbead-based multiplex assay. The patients showed significantly higher levels of serum IL-1β (p=0.033 and p=0.015), IL-6 (p<0.001), IL-8 (p<0.001 and p=0.002) and TNF-α (p=0.009 and p=0.005) than the TCE exposed workers and non-exposed controls. There was a significantly positive correlation among these cytokine concentrations, but no significant correlation was found between these cytokine concentrations and the disease duration in patient group. We further compared the effects of trichloroethanol (TCOH) and trichloroacetic acid (TCA), two major metabolites of TCE, on cytokine expression in keratinocyte cell line (HaCaT). IL-1α, IL-6, IL-8 and TNF-α concentrations were tested using enzyme-linked immunosorbent assay (ELISA) after HaCaT cells were treated with different concentrations of TCOH or TCA for 24h. We found that TCOH, but not TCA, increased the levels of IL-1α and IL-6 in a dose-dependent manner. We also found that TCOH activated the nuclear factor kappa B (NF-κB) pathway. Bay 11-7082 (NF-κB inhibitor) significantly attenuated the TCOH-induced production of IL-6 in HaCaT cells, but IL-1α production was not affected. In conclusions, it is suggested that IL-1β, IL-6, IL-8 and TNF-α were associated with TCE-induced hypersensitivity dermatitis. TCOH induced IL-6 expression through activation of the NF-κB pathway in HaCaT cells and may play an integral role in TCE-induced skin hypersensitivity.


Parent training for Attention Deficit/Hyperactivity Disorder: is it as effective when delivered as routine rather than as specialist care?
The effectiveness of parent training (PT) when delivered as part of specialist tier-two services for preschool AD/HD children has been recently demonstrated. To assess the effectiveness of the same PT programme when delivered as part of routine primary care by non-specialist nurses. A sample of 89 3-year-old children with preschool AD/HD took part in a controlled trial of an eight-week (one hour a week), health visitor delivered, PT package. Children, allocated randomly to PT (n = 59) and waiting list control (WLC; n = 30) groups, were compared. PT did not reduce AD/HD symptoms. Maternal well-being decreased in both PT and WLC groups. While PT is an effective intervention for preschool AD/HD when delivered in specialized settings, these benefits do not appear to generalize when programme are delivered as part of routine primary care by non-specialist nurses.


Perioperative glycemic control: use of a hospital-wide protocol to safely improve hyperglycemia.
Perioperative hyperglycemia impairs immunity and contributes to increased susceptibility to infection, higher incidence of multiorgan dysfunction, and greater mortality. Strict glycemic control is associated with lower infection rates, decreased length of stay (LOS), and faster recovery. A protocol that standardized preoperative education, testing, and treatment of elevated blood glucose (BG) safely improved perioperative glycemic control. Preoperative average BG improved from 191 to 155 mg/dL (P=.016); postoperative average BG decreased from 189 to 168 mg/dL (P=.094). The percentage of patients presenting with BG greater than 180 mg/dL preoperatively and achieving BG less than 180 mg/DL postoperatively increased from 21% to 43% (P = .09). Even though some results were statistically non-significant, the data showed a trend toward improvement with the new protocol. Good perioperative glycemic control, without an increased risk of hypoglycemia, is achievable.


Effects of infrared-LED illumination applied during high-intensity treadmill training in postmenopausal women.
Technology and physical exercise can enhance physical performance during aging. The purpose of this study was to investigate the effects of infrared-light-emitting diode (LED) illumination (850 nm) applied during treadmill training. Twenty postmenopausal women participated in this study. They were randomly divided into two groups. The LED group performed treadmill training associated with infrared-LED illumination (n=10) and the control group performed only treadmill training (n=10). The training was performed during 3 months, twice a week during 30 min at intensities between 85 and 90% of maximal heart rate. The irradiation parameters were 31 mW/cm(2), treatment time 30 min, 14,400 J of total energy and 55.8 J/cm(2) of fluence. Physiological, biomechanical, and body composition parameters were measured at the baseline and after 3 months. Both groups improved the time of tolerance limit (Tlim) (p<0.05) during submaximal constant-speed testing. The peak torque did not differ between groups. However, the results showed significantly higher values of power [from 56±10 to 73±8 W (p=0.002)] and total work [from 1,537±295 to 1,760±262 J (p=0.006)] for the LED group when compared to the control group [power: from 58±14 to 60±15 W (p≥0.05) and total work: from 1,504±404 to 1,622±418 J (p≥0.05)]. The fatigue significantly increased for the control group [from 51±6 to 58±5 % (p=0.04)], but not for the LED group [from 60±10 to 60±4 % (p≥0.05)]. No significant differences in body composition were observed for either group. Infrared-LED illumination associated with treadmill training can improve muscle power and delay leg fatigue in postmenopausal women.


Carboxymethylcellulose hybrid nanodispersions for edible coatings with potential anti-cancer properties.
Curcumin loaded lipid-polymer hybrid nanoparticles dispersions were fabricated from carboxymethylcellulose, stearic acid, polyethylene glycol and sesame oil using emulsion solvent evaporation method for their possible application as edible coatings for fresh vegetables and fruits. They were characterized by FTIR and TEM analysis. In addition, anti-bacterial, blood compatibility, cytotoxicity and anticancer studies were also carried out. The prepared nanodispersions showed excellent mixed nanostructured morphology with an average size of 94.96 nm. The hybrid nanodispersions showed excellent blood compatibility, non-toxicity and antitumor activity. The synthesized nanoparticle dispersion was employed as an edible coating solution for fresh apples and tomatoes. The hybrid system coated vegetables and fruits shows minimal weight loss after 15 days of storage. Hence, the formulated hybrid nanostructures of CMC are promising as edible coating solution, in addition to possessing the properties to fight cancer.


Characterization of middle-ear condition of Oporto daycare children up-to 3 years-old: a cross sectional study.
The aim of this study was to determine tympanometric values of children who attend Oporto daycare centers and further analyze any relations with host and environmental factors. Cross sectional study in a randomly selected sample of 117 daycare children up-to 3-years old from Oporto. Tympanometric measures were collected. Children presented in left ear (LE) a mean peak pressure (PP) of -156.53daPa and a mean compliance of 0.16cm(3). Right ear (RE) revealed a PP of -145.61daPa and a compliance of 0.19cm(3). Normal tympanograms (type A) had a lower frequency than abnormal tympanograms (type B and type C). There was a positive association between age and compliance (LE: p=0.016; RE: p=0.013) and between the presence of rhinorrhea and PP (LE: p=0.002; RE: p<0.05). Abnormal tympanograms were more frequent in Spring (RE: p=0.009), in younger children (LE: p=0.03) and in children that had rhinorrhea (LE: p=0.002; RE: p=0.044). Healthy children had a mean PP of -125.19daPa and a mean compliance of 0.21cm(3) in LE and a mean PP of -144.27daPa and a mean compliance of 0.22cm(3) in RE. Tympanometric measures presented in this paper may be applicable to Oporto daycare children up-to 3 years-old. Most of daycare children revealed abnormal tympanograms. Age, rhinorrhea and season influenced children's middle-ear condition.


Alternative behavioral approaches to the treatment of homosexuality.
Radical changes in attitudes toward homosexuality in American society are integrated into a new perspective for the therapist confronted by a client who engages in homosexual behavior. The traditional mandatory attempt to eradicate homosexual behavior has been expanded into three options, any one of which may be pursued by the therapist at the client's request: (1) modification of homosexual in favor of heterosexual behavior, (2) enhancement of homosexual behavior, and (3) ignoring of homosexual behavior if it is functionally unrelated to the presenting symptoms. Therapists' negative attitudes toward clients who engage in homosexual behavior are such as to abrogate expanded options and may results in therapeutic efforts at modification of homosexual behavior in defiance of the client's expressed wishes. Contrary to current professional belief, careful analysis and the use of appropriate techniques such as systematic desensitization, orgasmic reconditioning, and training in heterosocial skills generally obviate the necessity for aversive procedures in those instances where homosexual behavior is to be modified in favor of heterosexual behavior. Three case histories are presented illustrating the use of each of the expanded options described above.


Female homicides in United States workplaces, 1980-1985.
Women, while noted for low occupational injury mortality rates, are more likely to die as victims of assault than from any other manner of injury at work. From the National Traumatic Occupational Fatality surveillance data, 950 women were identified who were fatally assaulted at work. Homicide rates were calculated for the demographic and employment characteristics of these women. Risk ratios among types of lethal injuries were examined. During 1980-1985, the crude six-year workplace homicide rate was 4.0 deaths per million working women: one twentieth the homicide rate of the US female population. Decedents ranged from 16 years (the lowest age included in the data base) to 93 years of age. Working women older than 65 years had the highest age-specific homicide rate, 11.3 per million. Women younger than 20 had the lowest, 2.5 per million per year. Homicide rates for women of races other than White were nearly twice as high as those of Whites. The leading causes of death were gunshot wounds (64 percent), stabbings (19 percent), asphyxiations (7 percent), and blunt force trauma (6 percent). Nearly 43 percent of the deceased women had been employed in retail trade: 8.7 per million employed women annually. During 1980-1985, only 6 percent of the nation's victims of work-related injury deaths were female: 41 percent of those women were murdered. Homicide is currently the leading manner of traumatic workplace death among women in the United States.


Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort.
To characterize actual achieved patterns of oxygenation in infants born appropriate vs small for gestational age (SGA) randomized to a lower (85-89%) vs higher (91%-95%) oxygen saturation target in the Surfactant Positive Pressure and Oxygen Trial. To determine the association between achieved oxygen saturation levels and survival in infants born appropriate vs SGA enrolled in the Surfactant Positive Pressure and Oxygen Trial. Median oxygen saturation and intermittent hypoxemia events (<80%, 20 seconds-5 minutes) were documented in 1054 infants of 240/7-276/7 weeks of gestation while receiving supplemental oxygen during the first 3 days of life. Lower target infants who were small for gestational age had the lowest oxygen saturation and highest incidence of intermittent hypoxemia during the first 3 days of life. The lowest quartile of oxygen saturation (≤92%) during the first 3 days of life was associated with lower 90-day survival for both infants born appropriate and SGA. An increased incidence of intermittent hypoxemia events during the first 3 days of life was associated with lower 90-day survival only in infants born SGA. Lower achieved oxygen saturation during the first 3 days of life was associated with lower 90-day survival in extremely preterm infants. Infants born SGA had enhanced vulnerability to lower oxygen saturation targets as evidenced by lower achieved oxygen saturation and an association between increased intermittent hypoxemia events and lower survival. ClinicalTrials.gov: NCT00233324.


Healthcare professionals' knowledge and attitudes of surgical site infection and surveillance: A narrative systematic review.
This systematic review reports on healthcare professionals' knowledge and attitudes of surgical site infection and surgical site infection surveillance as well as interventions aimed at enhancing healthcare professionals' knowledge and attitudes. Surgical site infection is a serious adverse outcome following surgery. Despite the presence of international guidelines, the prevention of surgical site infections remains a challenge for patients and hospitals. It is critical that healthcare professionals have sufficient knowledge on surgical site infection and on their role in implementing evidence-based prevention strategies. This review is reported using the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. A search was undertaken in the following databases: Academic Search Complete, CINAHL, ERIC, MEDLINE, PsycARTICLES, PsycINFO and Web of Science for studies published between January 2010 and March 2022. Studies that examined healthcare professionals' knowledge and attitudes in relation to surgical site infection, surgical site infection surveillance and risk factors for their development were included. We also included studies that examined interventions that aimed to enhance healthcare professionals' knowledge and attitude in relation to surgical site infection, surveillance, and risk factors. We also described the impact of such interventions on the incidence of surgical site infections. A total of 26 studies were included. Results were synthesised narratively according to the review objectives. Findings from this review show that knowledge of what surgical site infection is and its prevention was poor amongst healthcare professionals, while attitudes were positive particularly in relation to healthcare professionals' role in prevention. Only three studies examined the effects of interventions on healthcare professionals' knowledge of surgical site infection and surgical site infection prevention. Of those, two used multimodal educational interventions and found statistically significant improvement in knowledge. Overall knowledge of surgical site infection and its prevention is poor amongst healthcare professionals, while attitudes were positive particularly in relation to healthcare professionals' role in prevention. There is a need for more experimental research to evaluate interventions which aim to address healthcare professionals' knowledge and attitudes towards surgical site infection prevention and surveillance. Such studies should include all healthcare professionals involved in the care of a surgical patient. Knowledge and attitudes of surgical site infection prevention amongst healthcare professionals.


Children's voices: qualitative data from the 'Barretstown studies'.
This paper describes the experiences of children (7-16 years) affected by life-threatening illness, attending a therapeutic recreation programme. In total, 240 children completed self-report questionnaires prior to the programme, with decreased response rates at follow-up. This paper focuses on children's responses to open-ended questions. The main findings showed that children's expectations focused on the activities and social interactions they were looking forward to, while some were concerned about being away from home. Also two-thirds felt that they had acquired personal and social functioning skills. These findings are discussed in relation to the value of qualitatively accessing children's views and experiences.


The Conformational Dynamics of Heterotrimeric G Proteins During GPCR-Mediated Activation.
Heterotrimeric G proteins (G proteins) are essential cellular signaling proteins that mediate extracellular signals to achieve various cellular functions. G-protein-coupled receptors (GPCRs) are the major guanine nucleotide exchange factors (GEFs) that induce G proteins to release guanosine diphosphate and rapidly bind to guanosine triphosphate, resulting in G protein activation. G proteins undergo dynamic conformational changes during the activation/inactivation process, and the precise structural mechanism of GPCR-mediated G protein activation is of great interest. Over the last decade, a number of GPCR-G protein complex structures have been identified, yet an understanding of the mechanisms underlying allosteric conformational changes during receptor-mediated G protein activation and GPCR-G protein coupling selectivity is only now emerging. This review discusses recent studies on the dynamic conformational changes of G proteins and provides insight into the structural mechanism of GPCR-mediated G protein activation.


Assemblage of dematiaceous and Ingoldian fungi associated with leaf litter of decomposing Typha latifolia L. (Typhaceae) in riverine wetlands of the Pampean plain (Argentina) exposed to different water quality.
The purpose of this study was to analyze the rate of sporulation, richness, and spore diversity of dematiaceous and Ingoldian fungi colonizing Typha latifolia leaves during a 40-day period of decomposition, as well as the loss of mass in Typha latifolia, in four riverine wetlands of Pampean plain (Argentina) with different water quality. Higher sporulation rates, richness, and diversity of the fungi as well as loss of mass of the leaves that they colonized were associated with lower water quality. Anguilospora longissima, Arthrinium sp., Margaritispora aquatica, and Tricellula botryosa were dominant taxa. Redundancy analysis showed two fungal assemblages related to different environmental conditions. One assemblage was related to higher nutrient levels and higher temperature, characterized mainly by dematiaceous fungi. The other assemblage was related to higher levels of pH and dissolved oxygen, which was mainly represented by Ingoldian fungi. The results obtained in our study demonstrated the link between these fungal assemblages and changes in water quality, revealing their potential as indicators of environmental changes in rivers exposed to different types of land use.


Sexual behavior problems in sexually abused children: a preliminary typology.
The goal was to develop an empirically derived typology for sexually abused children exhibiting sexual behavior problems to assist practitioners in differential assessment, treatment, and case planning. Data were systematically gathered from the clinical records of 100 sexually abused children, aged 3 years to 7 years, enrolled in two treatment programs. Twelve indexes were created corresponding to major areas of child and family history, functioning, and treatment response. After initial sorting into subgroups based on the presence or absence of interpersonal sexual behavior problems, further subdivision was based on hierarchical cluster analysis. Five distinctive sexual behavior profiles emerged: (1) developmentally expected; and developmentally problematic (2) interpersonal, unplanned, (3) self-focused, (4) interpersonal, planned (noncoercive), and (5) interpersonal, planned (coercive). Elements of the child's sexual abuse experience, opportunities to learn/practice problematic sexual behavior, and familial variables best differentiated between the types. The five types differed not only in child sexual behavior but in most areas of child and family functioning, including treatment outcome. The findings offer support for the development of an empirically-based typology for children with sexual behavior problems utilizing a range of variables which go beyond typical classification systems based on offender and victim characteristics.


Antispasmodic effects of flavoxate, MFCA, and REC 15/2053 on smooth muscle of human prostate and urinary bladder.
The antispasmodic effects of the flavone compounds flavoxate hydrochloride, 3-methylflavone carboxylic acid (MFCA), and REC 15/2053 (and in the case of the detrusor, oxybutynin), on the human detrusor, prostatic adenoma, prostatic capsule, and bladder neck, were studied by the in vitro isometric method. All the compounds inhibited, in different orders of potency, potassium-induced contractions of the tissues. Flavoxate showed a slightly greater activity than the other two compounds in the prostatic and bladder neck tissues. However, REC 15/2053 displayed greater activity in the detrusor than in the other tissues. The relaxant effect on the prostatic tissues suggests a potential use for these compounds in benign prostatic obstruction.


Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies.
Anti-CD20 monoclonal antibodies are promising for the treatment of B-cell malignancies such as chronic lymphocytic leukaemia and autoimmune diseases where auto-antibodies play an important role. Anti-CD20 such as rituximab (RTX) mediates B-cell depletion through mechanisms such as complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, in haematological malignancies, such effector mechanisms can be saturated and result in release of malignant B cells with reduced levels of CD20. It has been hypothesized that this is the result of monocyte-mediated shaving of the CD20/RTX complex from the B-cell surface. Here, we confirm, that in vitro co-culture of human monocytes and RTX-labelled syngeneic B cells results in reduced expression of CD20/RTX complex on the B cell surface. This shaving mechanism was the result of active protease activity because EDTA and PMSF were able to mediate partial inhibition. Also, a series of alternative anti-CD20 antibodies representing both type I and type II antibodies were tested for their ability to induce the shaving reaction. These results demonstrate that a monocyte-mediated shaving reaction can lead to complete loss of most anti-CD20 antibodies from the surface of B cells even from healthy donors and this is an important obstacle for antibody-mediated immune therapy. The findings demonstrate the necessity of developing novel antibodies that maintain high effector functions without enabling activation of the shaving reaction.


Crosslinked and PEGylated Pectin Chitosan nanoparticles for delivery of Phytic acid to colon.
Polysaccharide-based nanoparticles (NPs) such as pectin/ chitosan (PN/CN) had always been of greatest interest because of their excellent solubility, biocompatibility, and higher suitability for oral drug delivery. This study employed blending-crosslinking of polymers (PN&CN) followed by emulsification-solvent evaporation to prepare and compare two sets of PEGylated NPs to deliver phytic acid (IP6) to colon orally as it has potential to manage colon cancer but fails to reach colon when ingested in pure form. The first set was crosslinked with Glutaraldehyde (GE) (GE*PN-CN-NPs) while the second set was crosslinked with sodium tripolyphosphate (TPP) (TPP*PN-CN-NPs). IP6-loaded-GE/TPP*PN-CN-NPs were optimized using a central composite design. Developed TPP*PN-CN-NPs had a smaller size (210.6 ± 7.93 nm) than GE*PN-CN-NPs (557.2 ± 5.027 nm). Prepared NPs showed <12% IP6 release at pH 1.2 whereas >80% release was observed at pH 7.4. Further, NPs were explored for cytocompatibility in J774.2 cell lines, cytotoxicity, and cellular uptake in HT-29 and DLD-1 cell lines. While exhibiting substantial cytotoxicity and cellular uptake in HT-29 and DLD-1, the NPs were deemedsafe in J774.2. The PEGylated-TPP*PN-CN-NPs showed time-dependent uptake in J774.2 cell lines. Conclusively, the employed NP development method successfully delivered IP6 to colon and may also open avenues for the oral delivery of other drugs to colon.


COVID-19 knowledge, attitude, and practice of United Arab Emirates heath providers at the start of the pandemic 2020.
Early in 2020, healthcare providers faced the novel virus COVID-19 that had unprecedented risk to them and the community they serve. With COVID-19 high infectivity rate and considerable morbidity and mortality, healthcare providers ' precautionary practices to protect themselves, colleagues, and patients were determinantal to provide safe health services. This study aims to assess the knowledge, attitude, and practice of healthcare providers in the United Arab Emirates toward COVID-19 and to examine its determinants. This cross-sectional study was conducted to assess COVID-19 knowledge, attitudes, and practice (KAP) of healthcare providers in the Emirates of Abu Dhabi, the United Arab Emirates, from April to July 2020, using an online anonymous self-administered questionnaire. A convenient sampling method was used to distribute the online survey link through the organization's email network admin list and smartphone messaging. Descriptive statistics, t-tests, and multivariant linear regression were used. A total of 2371 healthcare providers responded to the survey. A total of 1091 worked in inpatient hospitals, 494 in primary health care, and 388 in emergency and ICU care. The overall performance score for all healthcare providers was as follows: 49.1%, poor score; 41.8%, intermediate score; and 9.2%, good score with a mean result of 17.14. Factors leading to better overall performance scores were years of experience, pediatricians' specialty, and specialist occupation. A total of 55.7% received good direct knowledge from all healthcare providers. In practice, 48% had good practices toward COVID-19. The overall attitude mean was 2.8, with a maximum score of 7, indicating a positive attitude toward COVID-19. Although this study describes a dynamic learning status and could reflect the early pandemic situation in Abu Dhabi health care, it does provide a method to assess the precursor of the critical outcome. It is recommended to follow this study with an assessment of the training program targeting all healthcare providers to ensure a better response to emerging infections.


Modeling human embryo development with embryonic and extra-embryonic stem cells.
Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical limitations in studying the natural human embryo, alternative approaches are needed to investigate mechanisms underlying this critical stage of human development. Here, we present an overview of the different stem cells and stem cell-derived models which serve as useful, albeit imperfect, tools in understanding human embryogenesis. Current models include stem cells that represent each of the three earliest lineages: human embryonic stem cells corresponding to the epiblast, hypoblast-like stem cells and trophoblast stem cells. We also review the use of human embryonic stem cells to model complex aspects of epiblast morphogenesis and differentiation. Additionally, we propose that the combination of both embryonic and extra-embryonic stem cells to form three-dimensional embryo models will provide valuable insights into cell-cell chemical and mechanical interactions that are essential for natural embryogenesis.


Marginal penetration of composite resin restorations as indicated by a tracer dye.
There was no evidence of marginal penetration of a tracer dye around Class V preparations lined with a BIS-GMA sealant, filled with Nuva-fil (a composite restorative material), and covered with the sealant. In the control group, 72 per cent of the Adaptic restorations showed varying degrees of marginal penetration.


Tetrahydro-beta-carboline micro-injected into the hippocampus induces an anxiety-like state in the rat.
Guide cannulae for bilateral micro-injection were implanted stereotaxically in the rat to rest just dorsal to the hippocampus. Following recovery, 1,2,3,4-tetrahydro-beta-carboline (THBC) hydrochloride in a concentration of 10 or 50 ng was infused bilaterally into the animal's hippocampus in a volume of 3.0 microliter. In the control condition, the artificial cerebrospinal fluid (CSF) vehicle was micro-injected into the hippocampus and a sham injection was made prior to the CSF or THBC infusion. The behavioral response of the rat was examined subsequently in an open-field chamber, in terms of the number of grid squares crossed, duration of grooming time and instances of freezing-immobilization during the test interval of 7.5 min. Other behaviors recorded included the appearance of tail rigidity and the number of fecal boluses excreted. The intra-hippocampal infusion of the 10 ng dose of beta-carboline reduced the motor activity of the rat whereas the higher dose of THBC increased the duration of the freezing-immobilization. THBC failed to alter significantly the grooming activity of rats or their rate of defecation. Following repeated micro-injections of 50 ng of THBC, the duration of freezing-immobilization gradually decreased, but the response itself remained essentially intact. These results suggest that the well-known anxiogenic action of certain of the beta-carboline class of aldehyde adducts may be mediated in part by neurons in the hippocampus, or the constituent pathways of this limbic system structure, or both.


Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer.
Endometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women's lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets. Differentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates. Twenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression. These findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.


Exercise-induced lowering of chemerin is associated with reduced cardiometabolic risk and glucose-stimulated insulin secretion in older adults.
To determine the effect of exercise on chemerin in relation to changes in fat loss, insulin action, and dyslipidemia in older adults. Thirty older (65.9±0.9yr) obese adults (BMI:34.5±0.7kg/m2). Single-center, Cleveland Clinic. Prospective clinical trial. Twelve-weeks of exercise training (60minutes/day, 5day/week at ~85% HRmax). Subjects were instructed to maintain habitual nutrient intake. Plasma chemerin was analyzed using an enzyme-linked immunosorbent assay. Peripheral and hepatic insulin sensitivity was assessed using a euglycemic-hyperinsulinic clamp with glucose kinetics. First-phase and total glucose-stimulated insulin secretion (GSIS) was calculated from an oral glucose tolerance test. Fasting blood lipids (cholesterol, triglycerides), total/visceral fat (dual-x-ray absorptiometry and computerized tomography) and cardiorespiratory fitness (treadmill test) were also tested pre and post intervention. Exercise increased fitness and reduced total/visceral fat, blood lipids, and first-phase GSIS (P<0.05). Training also increased peripheral insulin sensitivity and lowered basal/insulin-related hepatic glucose production (P<0.01). The intervention reduced chemerin (87.1±6.0 vs. 78.1±5.8ng/ml; P=0.02), and the reduction correlated with decreased visceral fat (r=0.50, P=0.009), total body fat (r=0.42, P=0.02), cholesterol (r=0.38, P=0.04), triglycerides (r=0.36, P=0.05), and first-phase and total GSIS (r=0.39, P=0.03 and r=0.43, P=0.02, respectively). Lower chemerin appears to be an important hormone involved in cardiometabolic risk and GSIS reduction following exercise in older adults.


Safety and efficacy of vitamin-based antioxidant therapy in patients with severe acute pancreatitis: a randomized controlled trial.
Oxidative stress plays a major role in the pathogenesis of pancreatitis. Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results. We wished to evaluate the efficacy and safety of antioxidant (vitamin A, vitamin C, vitamin E) therapy in patients with severe acute pancreatitis. This was a single-center, prospective, randomized, open-label with blinded endpoint assessment study of antioxidant therapy, conducted in the emergency department attached to our hospital. Thirty-nine patients with severe acute pancreatitis were randomly assigned to antioxidant treatment group (n=19) or a control group (n=20) within 96 hours of developing symptoms. Patients in the antioxidant group received antioxidants (vitamin A, vitamin E, vitamin C) in addition to the standard treatment provided to both the groups for a period of 14 days. The primary outcome variable was presence of organ dysfunction at day 7. The secondary outcome variables were length of hospital stay, multiorgan dysfunction (MODS) at day 7, recovery at the end of 4 weeks, complications, and mortality. The change in markers of oxidative stress from baseline was also measured. We demonstrated no significant difference in organ dysfunction (P=1.0), MODS (P=0.8), and length of hospital stay (P=0.29) between the two groups. All the patients survived in the antioxidant-treated group, whereas two patients died in the control group. The change in the levels of malondialdehyde, superoxide dismutase, and reduced glutathione were not significantly different in the two groups at day 7. Univariate analysis showed marginal benefit with antioxidant treatment (P=0.034) in patients with severe acute pancreatitis. This randomized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis.


The N-terminal disease-associated R5L Tau mutation increases microtubule shrinkage rate due to disruption of microtubule-bound Tau patches.
Regulation of the neuronal microtubule cytoskeleton is achieved through the coordination of microtubule-associated proteins (MAPs). MAP-Tau, the most abundant MAP in the axon, functions to modulate motor motility, participate in signaling cascades, as well as directly mediate microtubule dynamics. Tau misregulation is associated with a class of neurodegenerative diseases, known as tauopathies, including progressive supranuclear palsy, Pick's disease, and Alzheimer's disease. Many disease-associated mutations in Tau are found in the C-terminal microtubule-binding domain. These mutations decrease microtubule-binding affinity and are proposed to reduce microtubule stability, leading to disease. N-terminal disease-associated mutations also exist, but the mechanistic details of their downstream effects are not as clear. Here, we investigate the effect of the progressive supranuclear palsy-associated N-terminal R5L mutation on Tau-mediated microtubule dynamics using an in vitro reconstituted system. We show that the R5L mutation does not alter Tau interactions with tubulin by fluorescence correlation spectroscopy. Using total internal reflection fluorescence microscopy, we determined that the R5L mutation has no effect on microtubule growth rate, catastrophe frequency, or rescue frequency. Rather, the R5L mutation increases microtubule shrinkage rate. We determine this is due to disruption of Tau patches, larger order Tau complexes known to form on the GDP-microtubule lattice. Altogether, these results provide insight into the role of Tau patches in mediating microtubule dynamics and suggesting a novel mechanism by which mutations in the N-terminal projection domain reduce microtubule stability.


Combined EBSD/EDS tomography in a dual-beam FIB/FEG-SEM.
An automated method for collecting combined three-dimensional (3D) electron backscatter diffraction (EBSD)/energy dispersive spectroscopy (EDS) data sets on a dual-beam focused ion beam (FIB)/field emission gun scanning electron microscope (FEG-SEM) microscope is described. The method uses simple scripting files on the dual beam to move between the EBSD collection and the FIB slicing positions, which are linked to a commercial EBSD data collection programme. The EDS data are collected simultaneously with the EBSD patterns analogous to combined two-dimensional (2D) EBSD/EDS. The technique has been successfully applied to study both the interdiffusion zone between a coating and a substrate and a complex multi-phase coating on a nickel-based superalloy sample. This analysis is shown to enable the complex grain shapes, location of precipitates and phase interconnectivity within these samples to be determined without the ambiguities associated with 2D stereographic analysis.


EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy.
To analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE). Retrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR). Short-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality. The presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients. The present findings may help to improve the challenging prognosis estimation in HE patients.


An electrophile-nucleophile interaction in metalloprotein structures.
A new attractive interaction in metalloprotein structures, between the thiolate anion of a metal-bound cysteine (acting as a nucleophile) and a carbonyl carbon of a peptide group (an electrophile), has been identified. From 82 cases extracted from 23 metalloprotein structures, the interacting S and C atoms are found to be at a distance of 3.2 (+/-2) A, such that the angle S ... C-O is 109 degrees (+/-15 degrees). Usually, the interacting atoms are from the same Cys residue, and to allow the S to interact with the carbonyl group the side-chain and the main-chain torsion angles deviate from those found in cysteines not bound by metals. There is a good correlation between the S...C distance and the angular deviation of the S...C vector from the normal to the peptide plane. Various data points may be envisaged to represent "snapshots" along the reaction coordinate for the intra-residue attack of Cys S on the CO group.


Gastric vagal fibres distribution and acid secretion induced by portal infusion of D-glucose.
The vagal glucose signal pathway relevant to hepatic portal control of gastric acid secretion was examined in bilaterally adrenalectomized rats. The decrease in acid output after portal glucose injection was blocked by section of the hepatic branch which originates in the ventral vagus trunk below the diaphragm. After cervical vagotomy, the reduction in acid output was the same whether the section had been done on the right or the left side. The acid response was strongly inhibited by prior section of the dorsal vagus trunk at the celiac level. These results suggest that the hepatic glucose signal evoking an inhibitory action on the secretion of gastric acid has a specific pathway from the liver to the stomach, and that there is functional laterality in this pathway.


[Anatomy for the bronchologist: a prospective study of the normal endobronchial anatomic variants].
A comprehensive knowledge of the normal pattern of endobronchial branching is essential to any pulmonologist. The classification systems available are predominantly static descriptions and only seldom do they refer to possible variations within the normal spectrum. To evaluate all possible anatomical variants of the tracheobronchial tree we conducted a prospective study in our endoscopy unit between February, 1st and July, 10th (2009). A total of 181 individuals were included in the study. Anatomical variants were found to be present in 79 individuals (43% of total). Overall we found 20 different anatomical variants. Variations were more frequently found within the right upper lobe (16.6% of individuals). Middle lobe and lingula presented no variations. The variant most frequently found was the presence of a bifurcate pattern of the right upper bronchus (13.8%). The present study revealed a relatively high frequency of anatomical alternatives to the normal endobronchial branching pattern. Recognition of these variants and the frequency of their expression are fundamental for the bronchologist in establishing the limits of normal anatomy and preparing endobronchial techniques or surgical procedures.


Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.
The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.


Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern.
The cannabinoid CB(1)/CB(2) receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than approximately 840-fold CB(1)/CB(2) subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB(1)-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21.


Preparation of highly functionalized alkylzinc halides from alkyl bromides using Mg, ZnCl2 and LiCl.
Alkyl bromides bearing various functional groups are smoothly converted to functionalized alkylzinc reagents by the direct insertion of magnesium in the presence of LiCl and ZnCl(2).


Primary unilateral tuberculous inguinal lymphadenitis.
We report the case of a young Greek woman who presented with erythema nodosum and isolated unilateral inguinal lymphadenopathy. Excision and biopsy of the lymph node showed infection due to M. tuberculosis. An extensive workup did not reveal any other foci of tuberculosis. Isolated tuberculous inguinal lymphadenitis is a rare entity in developed countries and is almost always bilateral. Our case is unique because the disease was unilateral and affected an otherwise healthy woman who had never traveled in endemic areas.


Cortical modulation of neuronal activity in the cat's lateral geniculate and perigeniculate nuclei.
The cortico-thalamic influence on spontaneous and visually evoked activity of single cells in the dorsal lateral geniculate (LGN) and perigeniculate (PGN) nuclei were examined in unanesthetized cats with pretrigeminal brainstem transections by means of reversible cooling of cortical areas 17 and 18. The spatio-temporal characteristic of cells' RFs was tested with light spot randomly presented at different points along the receptive field axis. The cessation of cortical input decreased spontaneous activity of most of the LGN cells (64%; as compared to 36% with increased background firing). Similarly, their visually evoked responses were reduced (70% cells; compared to 24% with increased response) and extent of central excitatory domains diminished. In contrast, the majority of PGN neurons increased their spontaneous activity (62%; compared to 38% with decreased firing rate). Cortical cooling resulted also in a decrease of the ON and OFF central responses of most PGN cells (55%; as compared to 20% with increased responses). The described effects were more pronounced within the population of cells in X than in Y pathway. Although the removal of descending cortical excitation disturbed the balance of activity within the network of thalamic cells the gain of the geniculate relay was preserved. We conclude that the main role exerted by the cortico-thalamic pathway serves facilitation of the ascending retino-cortical flow of visual information at the level of lateral geniculate nucleus.


Genetic diversity and population structure of rice (Oryza sativa L.) landraces from Kerala, India analyzed through genotyping-by-sequencing.
Researchers stand at the vanguard of advancement and application of next-generation sequencing technology for developing dominant strategies for the sustainable management of genetically diverse crops. We attempt to fill the existing research lacuna in the molecular characterization of potent rice landraces in Kerala. Genotyping-by-sequencing (GBS) was performed on 96 Kerala rice accessions to identify single-nucleotide polymorphisms (SNPs), to examine the genetic diversity, population structure, and to delineate linkage disequilibrium (LD) pattern. GBS identified 5856 high-quality SNPs. The structure analysis indicated three subpopulations with the highest probability for population clustering with significant genetic differentiation, confirmed by principal component analysis. The genome-wide LD decay distance was 772 kb, at which the r2 dropped to half its maximum value. The analysis of genetic properties of the identified SNP panel with an average polymorphism information content (PIC) value of 0.22 and a minor allele frequency (MAF) > 0.1 unveiled their efficacy in genome-wide association studies (GWAS). High FST (0.266) and low Nm (0.692) portray a strong genetic differentiation among the rice landraces, complementing the genetic structuring observed in the studied population. Slow LD decay in the rice landraces reflects their self-pollinating behavior and the indirect selection of desired traits by domestication. Moreover, the high LD entails only a minimum number of SNP markers for detecting marker-trait association. The diverse germplasm utilized in this study can be further utilized to disclose genetic variants associated with phenotypic traits and define signatures of selection via GWAS and selective sweep, respectively.


MUC5AC expression is linked to mucinous/endometroid subtype, absence of nodal metastasis and mismatch repair deficiency in ovarian cancer.
Mucin 5AC (MUC5AC) is a secreted gel-forming mucin which is expressed by mucus producing cells of several organs but can also be found in cancer cells of the ovary, pancreas, and gastrointestinal tract. This study aimed to characterize the expression of MUC5AC and its potential prognostic implications in different ovarian cancer subtypes. MUC5AC expression was analyzed by immunohistochemistry on a tissue microarray containing 603 ovarian cancers. MUC5AC was commonly expressed in mucinous (27/36; 75%) and endometrioid (12/39; 31%) carcinomas, whereas malignant mixed Mullerian tumors (2/27; 7%), high-grade serous (20/373; 5%) and clear cell carcinomas (1/28; 4%) were only rarely MUC5AC positive and also showed lower expression levels. MUC5AC positive endometroid carcinomas and high-grade serous carcinomas lacked lymph node metastases (p = 0.0495 and p = 0.0216) suggesting a more favorable prognosis. Deficient mismatch repair (dMMR), associated with a favorable prognosis in different cancer types, was found in 4/39 (10%) MUC5AC positive cancers but in only 5/375 (1%) of MUC5AC negative cancers (p = 0.0052). In subgroup analyses MUC5AC positive endometroid carcinomas more frequently showed dMMR (4/10; 40%) as opposed to MUC5AC negative endometroid carcinomas (3/23; 13%; p = 0.0932). In summary, the results of our study show that MUC5AC expression is associated with mucinous and endometrioid ovarian carcinomas, lack of nodal metastases and dMMR. MUC5AC expressing ovarian cancers should be evaluated for dMMR.


Haemolytic and cytotoxic activities of the Tween 80-extracted putative haemolysin of Pasteurella multocida B:2.
The objective of this study was to investigate the haemolytic and cytotoxic activity of Pasteurella multocida B:2 strains, originally from cases of haemorrhagic septicaemia in cattle. All six P. multocida B:2 strains were non-haemolytic on sheep blood agar (SBA) and horse blood agar (HBA) when grown aerobically and on SBA anaerobically but they were haemolytic on HBA when grown anaerobically. No haemolytic activity against horse red blood cells was detected in culture supernates from aerobically or anaerobically grown cultures and only very weak haemolytic activity was obtained in supernates or pellet fractions from sonicated cells. However, after repeated extraction of sonicated cells with Tween 80, haemolytic activity was found in various cell fractions, both Tween-soluble and -insoluble. The Tween-extracted putative haemolysin and other bacterial fractions were also cytotoxic for mouse macrophage-like J774.2 cells. Further characterisation of the putative haemolysin revealed it to be a heat-labile, non-pore-forming protein of molecular weight >10 kDa whose activity was completely destroyed by trypsin and greatly reduced with protease and proteinase K treatment. Congo red also reduced the haemolytic activity. Non-denaturing gel-electrophoresis and RBC agar overlay revealed clear haemolytic zones but suggested that Tween was bound to some component of the P. multocida B:2 fractions and was responsible, to some extent, for the haemolytic activity observed. However, the effect of heat and other reagents on the Tween-extracted fractions and the lack of haemolytic activity in different Tween-extracted cell fractions of organisms other than P. multocida suggested that some proteinaceous component of the organism could indeed act as a haemolysin. This putative haemolysin may be one of the virulence attributes of P. multocida, but its characterisation and role in pathogenesis require further study.


The significance of some noninvasive methods in the objective evaluation of treatment of patients with coronary artery disease.
A measurement of STI and Bcg was used to provide an objective evaluation of the results of isosorbide dinitrate treatment of 120 patients suffering from coronary artery disease. Normalization of STI and Bcg in patients reporting subjective improvement following treatment was observed in a greater number of cases than the number with ECG normalization. Therefore, it can be concluded that after effective treatment measurement of STI AND Bcg provides a more sensitive means of objective evaluation than ECG.


Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice.
The recessive mutant mouse jumonji (jmj), obtained by a gene trap strategy, shows neural tube defects in approximately half of homozygotes with a Balb/cA and 129/Ola mixed background. Here, we show that no neural tube defects are observed with a Balb/cA background. We also found hypoplasia of the liver, thymus and spleen with full penetrance with a Balb/cA background. In the livers of homozygous embryos we found excessive cell death in the peripheral region. In both the thymus and spleen, the accumulation of hematopoietic cells is affected in mutant embryos. These phenotypes were also observed with C57BL/6J and DBA/2J backgrounds, suggesting that the jmj gene plays an essential role in the organogenesis of these tissues.


Co-electrospun poly(ɛ-caprolactone)/cellulose nanofibers-fabrication and characterization.
We report fabrication of poly (ɛ-caprolactone) (PCL)/cellulose (CEL) nanofiber blends via co-electrospinning for the possible use as biofilters and biosensor strips. Five different ratios of PCL to CEL were fabricated to investigate the wicking behavior. The cellulose acetate (CA) was taken as precursor to make cellulose nanofibers. Double nozzles were employed for jetting constituent polymers toward collector drum independently and resultant nanofibers webs were deacetylated in aqueous alkaline solution to convert CA into CEL as confirmed by FTIR spectra. FTIR further revealed that there is no effect of deacetylation on PCL nanofiber. The morphology of each blend webs under SEM showed uniform and bead-free nanofibers. Wicking behavior for five different ratios of PCL/CEL suggested that increasing CEL ratio in the blend enhanced the wicking front height; however, X-ray diffraction patterns of PCL/CEL showed a slight decrease in crystallinity.


The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing.
The complete nucleotide sequences of rat M1- and M2-type pyruvate kinase mRNAs were determined by sequencing the cDNAs and by analyses of S1 nuclease mapping and primer extension. The sequences have an identical molecular size of about 2220 nucleotides excluding a poly(A) tail and include 1593-nucleotide coding region. Their nucleotide sequences are identical except for 160-nucleotide sequences within the coding regions. The amino acid sequences of the M1- and M2-type subunits deduced from the cDNA sequences differ by only 45 residues within domain C, which constitutes the main region responsible for intersubunit contact. The sequence of this region of the M2-type shows higher homology than that of the M1-type with the corresponding sequence of the L-type. Since the M2- and L-types are allosteric enzymes, unlike to the M1-type, the residues common to the M2- and L-types, but not the M1-type may be important for mediating the allosteric properties. Genomic clones encoding both M1- and M2-type isozyme mRNAs were isolated. By partial sequence analysis of a clone lambda MPK37 four exons were identified, of which two adjacent exons coded the M1- and M2-specific sequences, respectively. The two remaining exons present downstream coded amino acids common to the two isozymes. Thus, we conclude that the M1- and M2-type isozymes of pyruvate kinase are produced from the same gene probably by alternative RNA splicing.


Computer-aided model-building strategies for protein design.
Model-building strategies for protein modification and design are developed. These strategies emphasize simple geometric aspects of protein structure, use local coordinate systems defined at particular residues, and systematically consider a large number of alternative sequences and conformations. We have written a computer program, PROTEUS, to implement these search methods. PROTEUS has been used to find positions where disulfide bonds could be added to the N-terminal domain of the lambda repressor and to predict how a loop on the surface of repressor could be shortened.


Extracellular polymeric substance from Rahnella sp. LRP3 converts available Cu into Cu5(PO4)2(OH)4 in soil through biomineralization process.
Soil contamination by toxic heavy metals such as copper is a serious problem. In this study, the extracellular polymeric substance (EPS) extracted from Rahnella sp. LRP3 was found with the potential of immobilizing Cu-polluted in soil. The EPS could bond to Cu (II) through functional groups (polysaccharides, amide, proteins, and carboxyl groups), which further developed into the porous sphere with a diameter of 20 μm. Besides, EPS could induce the formation of Cu5(PO4)2(OH)4 crystal by the biomineralization process. Finally, the EPS in the culture solution reduced 89.4 mg/kg of DTPA-Cu content by 78.99% in soil for 10 d under the condition of 25 °C via biomineralization. The results demonstrated that EPS produced by Rahnella sp. LRP3 will be a promising factor in the remediation of Cu contaminated soil.


Psychosocial determinants and family background in anorexia nervosa--results from the Stockholm Birth Cohort Study.
The aim of this study was to examine the associations between psychosocial factors and family background and incidence of anorexia nervosa (AN) in a Swedish cohort. The Stockholm Birth Cohort, SBC (N = 14,294) contains information on social background and general health in males and females, born in Stockholm 1953. Hospitalizations for AN, based on diagnoses from the ICD-8 through ICD-10, were recorded from 1969 to 2002. Cox proportional hazard regression was used to measure the association between psychosocial characteristics and family background and the risk of AN. Higher maternal education was associated with a higher risk for hospitalization for AN. An increased risk for AN was also found among females who stated that they "often compare their future prospects with others." Although the study is based on a low number of cases, it confirms earlier findings of higher maternal education among individuals with eating disorders in similar cohorts.


Preliminary detection of mites and coccidia with their zoonotic potential in meat-farmed rabbits in three districts in Selangor, Malaysia.
Mites infestation and gastrointestinal parasites including coccidia are common problems reported in pets, petting farms and farmed practices. Sarcoptes sp. and Cheyletiella sp. could be a potential zoonosis from rabbits to human. Detection of mites and coccidia with their zoonotic potential in meat-farmed rabbits from three (3) commercial farms in Selangor were investigated. Tape impression, fur pluck, skin scraping and ear swab tests were used for mites detection and faecal samples was used for coccidia examination by using McMaster's technique and the identification of Eimeria spp. was further analysed by sporulation technique. The overall prevalence of mites and Eimeria spp. (oocysts) in rabbits were 51.85% ± 0.38 (standard deviation; S.D.) and 76.47% ± 0.42 respectively. Sarcoptes scabiei was the most frequent mite found (25.92% ± 0.44), followed by Cheyletiella parasitovorax and Psoroptes cuniculi. Nine Eimeria spp. were identified and the oocysts of E. perforans shows the highest prevalence (64.71% ± 3.97) followed by E. exigua, E. coecicola, E. magna, E. flavescens, E. irresidua, E. intestinalis, E. media and E. stiedai. There was a significant difference (p = 0.013) where large-scale farm has a higher prevalence of coccidia than small scale farms apparently due to the excessive stocking density as coccidia are easily transmitted among rabbits through ingestion of sporulated oocysts. In conclusion, mites and coccidia are commonly present in the commercial rabbit farms, thus control and preventive measures should be executed to reduce the incidence of parasites. The zoonotic mites Sarcoptes scabiei and Cheyletiella parasitovorax detected in this study could be regarded as a public health concern especially when handling the rabbit.


Fractionation and characterization of lignins from Miscanthus via organosolv and soda pulping for biorefinery applications.
The structural complexity of lignins necessitates characterization and isolation methodologies for assessing their appropriateness for thermo-chemical systems and material applications. Lignins prepared via two pulping methods (organosolv and soda) were comprehensively investigated by analyzing the properties, including lignin purity, yield, and thermal and chemical properties. The extracted organosolv lignin has high purity (93.13-98.12%), however, the purity of soda lignin was relatively low (87.58-89.61%). Organosolv lignin produced the highest heating value of 26.79-26.95 MJ kg-1, with a fixed carbon content of 39.47-41.06 wt%, high purity, and low ash content, making it suitable for biofuel applications. The content of total phenolic OH groups was higher for the organosolv lignins; however, for the phenolic OH groups, the 4-vinylphenol content was significantly higher in the soda lignins, and increased with increasing NaOH concentration. Overall, the thermal and chemical properties related to the lignin structure changed with the fractionation method and solvent concentration, which in turn influences the design of lignin valorization strategies for prospective depolymerization and material applications.


Parallel evolution of pairs of dehydrogenase isoenzymes.
Lactate dehydrogenase and glycerol 3-phosphate dehydrogenase are metabolically coupled by the anaerobic dismutation of glyceraldehyde 3-phosphate and by the NAD redox state. This causes the concentrations of lactate and glycerol 3-phosphate to accumulate proportionally during anaerobic muscle contraction; these concentrations are high relative to those in aerobic tissues such as liver. We show that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken breast muscle have Km values for lactate and glycerol 3-phosphate, respectively, that are 10-fold higher than the Km values measured for the lactate dehydrogenase and glycerol 3-phosphate dehydrogenase isoenzymes from chicken liver. The association of proportionally higher Km values with the potential for proportionally higher accumulation of substrates suggests that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken muscle have evolved in parallel as a coupled metabolic unit distinct from the coupled isoenzymes in liver. The parallelism observed for the reduced substrates extends to the oxidized substrates, and to the coenzymes, NAD+ and NADH.


On electron transfer.
The tunneling transfer of electrons between two sites, appropriate to biological intermolecular electron transfer, contains physical considerations which are not important in the tunneling transfer between two metals. Analyses (such as the recent one by Hales) based on the well-known formula for the latter but applied to the former case are quantitatively and qualitatively misleading.


Interventional breast sonography.
This review article covers the basic applications of and latest developments in interventional breast sonography (US). For breast masses, US has become the standard for guiding needle biopsy, whether a fine needle or a core biopsy needle is used. US has also become the preferred method for guiding insertion of various localization devices for nonpalpable masses, and US's intraoperative use for this purpose is expanding. Recently, US has been used to monitor the placement of percutaneous ablation devices, such as radiofrequency ablation needle-electrodes, into breast masses, including carcinomas. US is not indicated for the routine evaluation of microcalcifications. However, on occasion, clusters of microcalcifications without a mass can be visualized on sonograms with sufficient clarity to undertake a US-guided core biopsy if stereotactically guided biopsy cannot be performed for technical reasons.


Domestic violence against elderly with disability.
Abuse against elders with disabilities is a growing problem as the world population ages. Though they require mandatory reporting, these cases are most frequently not detected or not reported by health professionals for a variety of reasons, including the difficulty of making an accurate diagnosis. By performing a retrospective analysis of alleged domestic violence cases against elders with moderate or severe disability, presented to medical forensic examination at the North Branch of the National Institute of Legal Medicine and Forensic Sciences of Portugal, in Porto, between 2005 and 2013 (n = 70), we aimed to improve our knowledge of some demographic and forensic characteristics of these cases as well as improve their detection and prevention. The most frequently reported type of abuse was physical (86%), allegedly perpetrated by male abusers (63%) living with their victims (90%), who were most commonly their children (47%) or partners (49%; when victims are married). The victims were most frequently female (63%) who had motor disabilities (49%) and presented a history of previous episodes of abuse in 74% of cases; however, only 28% were previously reported. The physical consequences were most frequently minor injuries (95%) with permanent consequences (scars) in only 6.8% of the cases. The injuries were multiple in the majority of the cases (64%), and the preferred locations were the head and neck (75%). Elderly females with motor disabilities appear to have a greatest risk of domestic violence, which translates, most frequently, into multiple injuries that are mainly in the head and neck.


Early amniocentesis and amniotic fluid organic acid levels in the prenatal diagnosis of organic acidemias.
Organic acids were studied in amniotic fluids taken by early amniocentesis between 6 to 12 weeks in control pregnancies. The prenatal diagnosis of methylmalonic acidemia and propionic acidemia could be made by the measurement of methylmalonic and methylcitric acid respectively in the amniotic fluid taken simultaneously with chorionic villi at the 11th week of gestation.


Squamous cell carcinoma of the lower lip.
Most patients with squamous cell carcinoma of the lower lip present with early disease and follow a rather indolent clinical course. Determinant 5-year survival rates range from 85% to 95%. This study was undertaken in an attempt to gain insight into the cause of failure in those few patients who develop recurrent disease. A retrospective review was completed on patients treated between 1964 and 1990. Patients were staged according to the American Joint Committee. Patients with no palpable adenopathy had either a unilateral or bilateral suprahyoid dissection performed. Patients with palpable adenopathy underwent radical neck dissection. All patients were followed for evidence of recurrent disease. The records of 92 patients treated surgically for squamous cell carcinoma of the lower lip were available and complete. Palpable adenopathy was present in 38 patients; however, only 8 of these patients (21%) were histologically positive. Of the 54 patients judged to be free of disease, 3 (5.5%) had histologic evidence of metastasis. Overall, the incidence of cervical metastasis was 12%. The incidence of cervical metastasis in patients with squamous cell carcinoma of the lip is low; however, these data suggest that the size of the primary tumor does not correlate closely with predicting the incidence of regional lymph node metastases.


Is there an association between female urinary incontinence and decreased genital sensation?
To explore the relationship between urinary incontinence and genital sensory functioning in females with sexual dysfunction disorders. A retrospective consecutive chart review was conducted for all women who were referred to our tertiary female urology clinic with a primary complaint of sexual dysfunction between October 1999 and January 2009. Our study sample included 177 women, all of whom underwent a thorough clinical evaluation. Urinary incontinence was diagnosed based on clinical history and physical examination by a urogynecologist. The Genital Thermal and Vibratory Sensory Analyzer (GSA) was used for sensory testing in the genital area. Independent t-test and multivariate linear regression were used for statistical analysis. Of the 177 study patients (median age 34, range 18-68), 63 (36%) had urinary incontinence. Women with urinary incontinence were found to be less sensitive to warm, cold, and vibratory thresholds at both the anterior and the posterior vaginal wall and the clitoral area (P < 0.05). Women with urinary incontinence and sexual dysfunction are less sensitive to all sensory testing in the genital region than women with sexual dysfunction alone. This relationship may be attributable to afferent nerve damage and the critical role it may play in the etiology of urinary incontinence.


Early self-reported impairments in arm functioning of primary breast cancer patients predict late side effects of axillary lymph node dissection: results from a population-based cohort study.
Improvements in the life expectancy of women with breast cancer raise important questions how to improve quality of life (QoL) for women sustaining complications and side effects of cancer treatment. The presented study examined the prevalence of arm morbidity in a cohort of primary breast cancer patients over time as a result of the extent of axillary lymph node dissection. Of particular interest is the question of using a recognized QoL assessment instrument at defined assessment points as an endpoint criteria of oncological treatment. A prospective, population-based, longitudinal cohort study of patients with primary breast cancer was performed (n = 389). QoL data (EORTC QLQ C30 + BR23) and clinical data were assessed at designated time points. Primary endpoint of this analysis was patient reported arm morbidity assessed with the three-idem scale in the BR 23 (swelling, moving, pain). 20% of the patients evidenced considerable impairments in arm functioning. Arm morbidity was significantly related to the number of lymph nodes dissected (P < 0.002 entire cohort, P < 0.001 lymph node negatives) and was independent of age, stage of the disease, kind of breast surgery and radiation treatment. Early impairments in arm functioning (below 50 score values) assessed within 6 months after axillary surgery was a good predictor for late arm morbidity at 12 months RR 11.5 (CI 95% 4.7-28.4), 24 months RR 6.0 (CI95% 2.8-13.3) and 36 months RR 3.8 (CI 95% 1.8-7.9). Arm morbidity after axillary surgery is a severe and chronic condition affecting many breast cancer patients. The recognized QoL assessment instrument depict patients with severe impairments in arm functioning after axillary lymph node dissection and predict late arm morbidity. To increase patients' quality of life it thus may serve as a valid assessment tool for screening, allowing early referral for treatment and monitoring.


Artificial intelligence scoring of liver biopsies in a phase ii trial of semaglutide in non-alcoholic steatohepatitis.
Artificial intelligence-powered digital pathology offers the potential to quantify histologic findings in a reproducible way. This analysis compares the evaluation of histological features of non-alcoholic steatohepatitis (NASH) between pathologists and a machine learning (ML) pathology model. This post hoc analysis included data from a subset of patients (N=251) with biopsy-confirmed NASH and fibrosis stage F1-F3 from a 72-week randomised placebo-controlled trial of once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg (NCT02970942). Biopsies at baseline and week 72 were read by two pathologists. Digitised biopsy slides were evaluated by PathAI's NASH ML models to quantify changes in fibrosis, steatosis, inflammation, and hepatocyte ballooning using categorical assessments and continuous scores. Pathologist and ML-derived categorical assessments detected a significantly greater percentage of patients achieving the primary endpoint of NASH resolution without worsening of fibrosis with semaglutide 0.4 mg vs placebo (pathologist 58.5% vs 22.0%, p <0.0001; ML 36.9% vs 11.9%; p=0.0015). Both methods detected a higher but non-significant percentage of patients on semaglutide 0.4 mg vs placebo achieving the secondary endpoint of liver fibrosis improvement without NASH worsening. ML continuous scores detected significant treatment-induced responses in histologic features, including a quantitative reduction in fibrosis with semaglutide 0.4 mg vs placebo (p=0.0099) that could not be detected using pathologist or ML categorical assessment. ML categorical assessments reproduced pathologists' results of histological improvement with semaglutide for steatosis and disease activity. ML-based continuous scores demonstrated an antifibrotic effect not measured by conventional histopathology.


Effect of Abamectin on Fungal Growth and Its Efficacy as a Miticide in the Laboratory.
Abamectin was tested for use with solid agar media in the laboratory to eliminate or kill the common mold mite Tyrophagus spp. in fungal cultures of Phaeomoniella chlamydospora and Phaeoacremonium minimum, two important grape pathogens involved in grapevine trunk disease. Abamectin concentrations tested were at or below the recommended dosage for abamectin in greenhouse spray applications (≤625 µg/ml) to control mites and determine the following: (i) if fungal growth would be inhibited and (ii) if mites would be killed or their activity suppressed. Abamectin was either added to the media before autoclaving or filter-sterilized and added after autoclaving to test the effects of autoclaving on abamectin efficacy. Streptomycin (100 µg/ml) was also added to a set of treatments to determine whether this commonly used antibiotic would affect abamectin efficacy against mites or have an effect on fungal growth when combined with abamectin. Filter-sterilized abamectin in the range of 62.5 to 312 µg/ml, delivered to the media after autoclaving, provided the most effective control of mites while also showing limited inhibition of fungal growth on solid agar media in the absence of streptomycin. The addition of filter-sterilized streptomycin had no significant effect on fungal growth for Phaeomoniella chlamydospora, whereas for Phaeoacremonium minimum a small but significant reduction in growth with streptomycin occurred at abamectin concentrations >62.5 µg/ml.