Fabrication of direct Z-scheme Cu2O@V-CN (octa) heterojunction with exposed (111) lattice planes and nitrogen-rich vacancies for rapid sterilization.
The Z-scheme heterojunction has demonstrated significant potential for promoting photogenerated carrier separation. However, the rational design of all-solid Z-scheme heterojunctions catalysts and the controversies about carrier transfer path of direct Z-scheme heterojunctions catalysts face various challenges. Herein, a novel heterojunction, Cu2O@V-CN (octa), was fabricated using V-CN (carbon nitride with nitrogen-rich vacancies) in-situ electrostatic self-wrapping Cu2O octahedra. Density functional theory (DFT) calculations revealed that the separation of carriers across the Cu2O@V-CN (octa) heterointerface was directly mapped to the Z-scheme mechanism compared to Cu2O/V-CN (sphere). This is because the Cu2O octahedra expose more highly active (111) lattice planes with more terminal Cu atoms and V-CN with abundant nitrogen vacancies to form delocalized electronic structures like electronic reservoirs. This facilitates the wrapping of Cu2O octahedra by V-CN and protects their stability via tighter interfacial contact, thus enhancing the tunneling of carriers for rapid photocatalytic sterilization. These findings provide novel approaches for designing high-efficiency Cu2O-based photocatalytic antifoulants for practical applications.


[Changes in the TNM classification of gynecological tumors].
Based on the results of clinical and histomorphological studies in recent years, a revision of the TNM classification of malignant tumours of the female genital organs became necessary. Vulvar cancer saw the most significant changes. In the T1 category the new system recognises tumour size and its relation to the infiltration of adjacent structures by the tumour. The number of positive regional lymph nodes has also been included in the new staging system. For cervical cancer, there is a new subdivision of the category T2a depending on tumour size with a breakpoint of ≤ 4 cm versus > 4 cm and a subdivision into T2a1 und T2a2. In endometrial cancer, the previous pT1a and pT1b were merged to pT1a. The former category T1c has changed into T1b. The category pT1c is no longer used. For the first time, there is a TNM classification system for uterine sarcomas.


Isolation of viruses from sewage, with special regard to poliovirus: an evaluation of the sensitivity of three tissue culture methods.
This report concerns experiments to isolate different viruses from sewage. Using a special cell-line from Utrecht, derived from human amniotic cells, it was possible to isolate poliovirus selectively when antisera against six types of coxsackievirus B were added to the tissue culture. The method was tested in connexion with the epidemiological investigation of a case of poliomyelitis in Sweden in 1977. It rapidly demonstrated that the virus implicated was present in all neighbouring sewage plants, indicating a wide distribution of the virus in the area.


Diuretic radionuclide urography: a non-invasive method for evaluating nephroureteral dilatation.
The diuretic radionuclide urogram is a simple, rapid and non-invasive technique to determine whether true obstruction exists in dilated nephroureteral systems. The methodology, results and interpretation of 102 studies in 41 patients are presented and compared to the conventional methods of assessing hydroureteronephrosis.


Poor perception of chronic kidney diseases and its influencing factors among diabetics patients.
Purpose We aimed to determine predictors of chronic kidney disease (CKD) prevention among patients with diabetes. Method A cross-sectional study was conducted on 1000 selected respondents based on socio-demographic, socio-economic, general CKD perception knowledge, self-monitoring advocacy, preventive behavior, treatment compliance, and psychosocial factors. Using multiple logistic regression, variables and their association with impaired perception of CKD prevention were analyzed. Results Overall, 74% had poor perception regarding CKD prevention (68.7% of men and 31.3% of women). In multivariable analysis, those with weak illness identity fear were two times more likely to have poor perceptions (95% CI 1.563-3.196, p < 0.001). Respondents with weak medical practice (AOR = 2.33, 95% CI 1.609-2.381, p < 0.001) and weak cooperation (AOR = 1.563; 95% CI 1.099-2.224, p < 0.001) were more likely to have poor perceptions on CKD prevention. Concerning poor perception, significant predictors were self-employment, housewives, working in private jobs, weak knowledge on clear glycosuria, sleep problems, print media, digital media, illness identity fear, weak medical practice, and weak co-operation factors. Conclusion Media support is crucial for supporting and improving positive views regarding CKD knowledge. Interventions to reach people with limited awareness on CKD prevention, lower socioeconomic status, and poor social support may improve identification of patients with early-stage CKD. Particular care should be taken to recognize and provide necessary services regarding the early detection of CKD.


CNN-LSTM deep learning based forecasting model for COVID-19 infection cases in Nigeria, South Africa and Botswana.
COVID-19 pandemic has indeed plunged the global community especially African countries into an alarming difficult situation culminating into a great deal amounts of catastrophes such as economic recession, political instability and loss of jobs. The pandemic spreads exponentially and causes loss of lives. Following the outbreak of the omicron new variant of concern, forecasting and identification of the COVID-19 infection cases is very vital for government at various levels. Hence, having knowledge of the spread at a particular point in time, swift actions can be taken by government at various levels with a view to accordingly formulate new policies and modalities towards minimizing the trajectory of the consequences of COVID-19 pandemic to both public health and economic sectors. Here, a potent combination of Convolutional Neural Network (CNN) learning algorithm along with Long Short Term Memory (LSTM) learning algorithm has been proposed in this work in order to produce a hybrid of a deep learning algorithm Convolutional Neural Network - Long Short Term Memory (CNN-LSTM) for forecasting COVID-19 infection cases particularly in Nigeria, South Africa and Botswana. Forecasting models for COVID-19 infection cases in Nigeria, South Africa and Botswana, were developed for 10 days using deep learning-based approaches namely CNN, LSTM and CNN-LSTM deep learning algorithm respectively. The models were evaluated on the basis of four standard performance evaluation metrics which include accuracy, MSE, MAE and RMSE respectively. However, the CNN-LSTM deep learning-based forecasting model achieved the best accuracy of 98.30%, 97.60%, and 97.74% for Nigeria, South Africa and Botswana respectively; and in the same manner, achieved lesser MSE, MAE and RMSE values compared to models developed with CNN and LSTM respectively. Taken together, the CNN-LSTM deep learning-based forecasting model for COVID-19 infection cases in Nigeria, South Africa and Botswana dramatically surpasses the two other DL based forecasting models (CNN and LSTM) for COVID-19 infection cases in Nigeria, South Africa and Botswana in terms of not only the best accuracy of with 98.30%, 97.60%, and 97.74% but also in terms of lesser MSE, MAE and RMSE.


Haematoloechus medioplexus: light and electron microscope localization of dipeptidyl aminopeptidases I and II in the gastrodermis.
The exopeptidases, dipeptidyl aminopeptidases I and II (EC 188.8.131.52 and EC 126.96.36.199, respectively) were demonstrated cytochemically at light and electron microscope levels in the gastrodermis of adult Haematoloechus medioplexus recovered from the lungs of naturally infected Rana pipiens. Lys-Ala-4-methoxy-beta-naphthylamide and Pro-Arg-4-methoxy-beta-naphthylamide were used as specific substrates. Reaction products from both enzymes were observed in the gastrodermis in what are believed to be vesicles analogous to secondary lysosomes. The localization of the enzymes in these vesicles coincides with previous reports of the distribution of acid phosphatase and esterase activities. The hydrolases are believed to function both intracellularly by autophagy and extracellularly by digestion of host globin in the cecal lumen. Cathepsin B activity was not observed following the cytochemical protocol used in this investigation.


[Evaluation of the treatment with disodium cromoglycate in the ulcerative rectocolitis. Our experience].
This study highlights the possibility of treating recidivating ulcerative rectocolitis with oral disodium cromoglycate based on the assay of plasma IgE. The study was performed from January 1995 to December 1997 in 28 patients suffering from recidivating ulcerative rectocolitis whose main symptom was hematic diarrhoea. Total plasma IgE were assayed in all patients and oral disodium cromoglycate treatment was commenced at a dose of 1.500 mg pro/die with follow-up at 2, 6, 12 and 24 months to evaluate general and endoscopic clinical conditions. Patients with a high titre of total IgE showed a full remission of symptoms and no recidivation. The authors conclude by emphasising the importance of immunological factors in the pathogenesis of the disease and underline the stabilising effect of oral disodium cromoglycate on mast cells.


Successful Treatment of Chronic Hepatitis C Infection With Direct-Acting Antivirals in a Heart Transplant Recipient: A Case Report.
Heart transplant (HT) recipients with chronic hepatitis C virus (HCV) infection are noted to have higher rates of HCV related morbidity and mortality. Treatment of HCV in the past was fraught with low cure rates, increased risk of graft rejection, and medication-related side effects. We report a case of successful treatment of HCV infection in a HT recipient. The patient was found to have HCV during his pretransplant workup. He underwent uneventful orthotopic HT in 2000. The HCV infection was monitored with regular liver enzymes and the surveillance liver biopsies at 2 and 5 years after HT showed mild but stable liver disease, and he stayed on chronic immunosuppression. He was not offered interferon-based HCV therapy because of the risk of steroid-resistant graft failure and cardiac decompensation. With the availability of the new direct-acting antivirals (DAA) for HCV infection, and worsening of liver fibrosis on noninvasive testing, we treated him with sofosbuvir and simeprevir for 12 weeks. During treatment, he remained clinically stable from a cardiac standpoint and he showed biochemical improvement in his liver and renal functions. Tacrolimus levels remained stable and did not require any dose adjustment. He showed rapid virologic response and subsequently achieved sustained virologic response at 12 weeks. DAA use was safe and effective in treating HCV infection in a HT recipient.


Aldosterone and prolactin responsiveness after prolonged treatment of congestive heart failure with captopril.
After long-term captopril treatment, an inappropriate increase in aldosterone levels has been observed in hypertensive patients. It is not known, whether a similar change would occur in patients with severe congestive heart failure, and whether it is due to a decrease in endogenous dopaminergic inhibition of aldosterone secretion or to aldosterone stimulation by ACTH or an ACTH-related peptide. Therefore, the aldosterone and prolactin responses to metoclopramide have been studied in 10 patients with severe congestive heart failure (NYHA Class III or IV) after 6 months of captopril treatment, before and 11 h after pretreatment with dexamethasone. 7 placebo-treated patients served as double-blind controls. In captopril-treated patients, the supine aldosterone levels exceeded the normal range and were as high as in placebo-treated patients. The responsiveness of aldosterone and prolactin to metoclopramide was not influenced by captopril. Only in the placebo group were the aldosterone levels decreased by dexamethasone. Captopril increased plasma renin activity and serum potassium, and decreased supine epinephrine and norepinephrine and serum sodium. Thus, previous reports of inappropriately high aldosterone levels after long-term captopril treatment were confirmed in patients with severe congestive heart failure. It is concluded that increased aldosterone is due neither to a decrease in endogenous dopaminergic inhibition nor to dexamethasone-suppressible stimulation of aldosterone secretion.


Squaric monoamide monoester as a new class of reactive immunization hapten for catalytic antibodies.
A squaric monoester monoamide motif was employed as an effective reactive immunogen for the discovery of monoclonal antibodies with reactive residue(s) in their combining sites. Two antibodies, 2D4 and 3C8, were uncovered that enhance paraoxon hydrolysis over background. Kinetic analysis of these antibodies was performed and interestingly both undergo a single turnover event due to covalent modification within the antibody combining site. Because antibodies 2D4 and 3C8 result in covalent attachment and thus inactivation of paraoxon, they could be useful probes for investigating paraoxon intoxication.


Chemical signals of elephant musth: temporal aspects of microbially-mediated modifications.
Mature male African (Loxodonta africana) and Asian (Elephas maximus) elephants exhibit periodic episodes of musth, a state in which serum androgens are elevated, food intake typically decreases, aggressiveness often increases, and breeding success is enhanced. Urine is a common source of chemical signals in a variety of mammals. Elephants in musth dribble urine almost continuously for lengthy periods, suggesting that the chemicals in their urine may reveal their physiological condition to conspecifics. We investigated the volatile urinary chemicals in captive male elephants using automated solid phase dynamic extraction (SPDE) and gas chromatography-mass spectrometry (GC-MS). We found higher levels of alkan-2-ones, alkan-2-ols, and some aromatic compounds in urine from males in musth than in urine from non-musth males or from females. Levels of ketones and alcohols increased as the urine aged, likely due to microbial metabolism of fatty acids. Protein-derived aromatic metabolites also increased in abundance after urination, likely due to microbial hydrolysis of hydrophilic conjugates. We suggest that microbes may play an important role in timed release of urinary semiochemicals during elephant musth.


Dichaptic-visual form matching in adults.
Although previous visuo-dichaptic matching studies report hemispheric asymmetries in spatial-form perception, more recent studies have failed to support these findings. Three cross-modal matching experiments examined hemispheric asymmetries in adult spatial-form matching. In the first experiment, subjects simultaneously felt two eight-point or 12-point tactile shapes patterned after Vanderplas and Garvin (1959) for four seconds and were then required to identify both shapes from a visual response array. Results showed subjects were significantly better identifying eight point shapes. A marginally significant feeling hand by pointing hand interaction indicated that recognition accuracy was higher when shape ipsilateral to the pointing hand was identified. In the second experiment, only one of the two tactile shapes had to be identified from the visual array. Results showed a significant interaction between complexity and feeling hand, where the left and right feeling hands were respectively better at identifying 12-point and eight-point shapes. The third experiment was an attempt to more directly examine the Witelson (1976) experiment using her spatial-form stimuli. Results showed no significant laterality nor stimulus-response compatibility effects. These findings are discussed in terms of cerebral asymmetry and stimulus-response compatibility models.


In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease.
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.


Assembly and disassembly dynamics of the cyanobacterial periodosome.
In vitro incubation of three Kai proteins, KaiA, KaiB, and KaiC, with ATP induces a KaiC phosphorylation cycle that is a potential circadian clock pacemaker in cyanobacterium Synechococcus elongatus PCC 7942. The Kai proteins assemble into large heteromultimeric complexes (periodosome) to effect a robust oscillation of KaiC phosphorylation. Here, we report real-time measurements of the assembly/disassembly dynamics of the Kai periodosome by using small-angle X-ray scattering and determination of the low-resolution shapes of the KaiA:KaiC and KaiB:KaiC complexes. Most previously identified period-affecting mutations could be mapped to the association interfaces of our complex models. Our results suggest that the assembly/disassembly processes are crucial for phase entrainment in the early synchronizing stage but are passively driven by the phosphorylation status of KaiC in the late oscillatory stage. The Kai periodosome is assembled in such a way that KaiA and KaiB are recruited to a C-terminal region of KaiC in a phosphorylation-dependent manner.


Perioperative Bioccipital Watershed Strokes in Bilateral Fetal Posterior Cerebral Arteries During Spinal Surgery.
Vision loss due to cerebral infarction during spinal surgery is less described. Intraoperative hypotension would be a leading cause. Patients with variation of the circle of Willis could be more prone to present stroke in this context, but reports are lacking to sustain the theory. Bilateral occipital watershed ischemic strokes have never been described before. We report the case of a patient with a fetal origin of both posterior cerebral arteries (PCAs), presenting this particular anatomic stroke following lumbar laminectomy surgery for spinal stenosis during which intraoperative hypotension was observed. We discuss how this common anomaly associated with intraoperative hypotension could have promoted this serious complication. A 55-year-old man woke up with cortical blindness after he had undergone lumbar surgery during which a marked decrease in blood pressure had occurred. Magnetic resonance imaging revealed bilateral symmetric infarctions of the occipital lobes in the distal territory of both PCAs and smaller anterior watershed ischemic strokes, suggesting a hemodynamic mechanism. Extended investigations, including conventional angiography, failed to find any cause of stroke but revealed bilateral fetal PCAs supplied by internal carotid arteries only. Two years later, the patient has not recovered and remains severely visually impaired. The standing hypothesis would be posterior low-flow infarctions resulting from intraoperative hypotension on a variation of the circle of Willis more prone to decrease in cerebral blood flow. Moreover, this case supports the hypothesis of vascular insufficiency due to intraoperative hypotension as cause of stroke during spinal surgery.


Effect of sugarcane molasses extract on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system.
Molasses, the main by-product of sugar production, is a well-known source of antioxidants. In this study, sugarcane molasses extract was investigated for its total phenolic content and in vitro antioxidant capacity. The experimental total phenolic content was 101.3 mg of gallic acid equivalent (GAE) in 1 g of extract, IC50 of Trolox and sugarcane molasses extract were 125.33 μg/ml and 126.0 μg/ml, respectively. A chemical model system showed that the sugarcane molasses extract effectively reduced the formation of phenylacetaldehyde and the aldol condensation product, meanwhile, the amount of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) also decreased. This could be due to the reaction between the phenolic compounds of sugarcane molasses extract and the carbonyl group of phenylacetaldehyde inhibiting the aldol condensation product formation, and this would suppress the formation of PhIP. A pathway that phenolic compounds inhibited the formation of PhIP is proposed. This pathway also suggested a mechanism for how the sugarcane affects the formation of PHIP.


Regional cerebral energy metabolism in bicuculline induced seizures.
In order to assess the early regional changes in energy metabolism in bicuculline induced seizures, mice were injected and sacrificed before the onset of overt seizure activity, and shortly after clonic-tonic seizures began. The energy metabolites glucose, ATP, and phosphocreatine were measured in layers of the motor cortex and the cerebellar vermis. Results showed minimal metabolite changes in the cerebellum, whereas changes in energy metabolism in the motor cortex were largely localized to the layers containing pyramidal cells. These results are in agreement with previous studies showing a relative sparing of the cerebellum, and suggest early cortical changes occur in pyramidal cells.


Predictors and Consequences of Silent Brain Infarction in Patients with Asymptomatic Carotid Stenosis.
Silent brain infarction (SBI) is associated with an increased risk of stroke in patients with asymptomatic carotid stenosis (ACS), and is therefore one of the criteria for performing carotid endarterectomy (CEA). Despite an extensive literature, this issue is still a matter of debate. Aim of the present work was to evaluate incidence and predictors of SBI in patients undergoing CEA for ACS, and to investigate its possible impact on CEA outcome. All patients submitted to CEA in a single academic center from 2005 to 2019 were prospectively inserted into a specific database. The presence of SBI was evaluated by preoperative computed tomography (CT), considering exclusively infarctions in the carotid territories from an athero-embolic source. Preoperative characteristics were investigated as possible risk factor for SBI at the uni- and multivariate analysis. The impact of SBI on stroke occurrence after CEA was also evaluated. In the designated period, over a total of 1288 ACS considered and submitted to CEA, 105 (8.2%) were associated with SBI. Male sex, hypertension, dyslipidaemia, smoking, contralateral carotid occlusion and severity of carotid stenosis were associated with SBI at the univariate analysis; preoperative statin therapy showed to be a protective factor. At the multivariate analysis, contralateral carotid occlusion and severity of stenosis were independently associated with SBI (OR: 3.16, 95%CI 1.62-6.18, P=.001; OR: 1.04, 95%CI 1.01-1.07, P=.004, respectively), with statin therapy confirmed as a protective factor (OR: 0.60, 95%CI: 0.40-0.92, P=.002). Overall post-CEA stroke rate was 0.9%, with a higher post-operative risk independently predicted by the presence of SBI (OR:4.23, 95%CI: 1.40-12.73, P=.01). SBI is present in 8% of patients with ACS, and is significantly associated with contralateral carotid occlusion and severity of the carotid stenosis. Statin therapy reduces the occurrence of this phenomenon. The presence of SBI should be carefully considered in indication to CEA since it significantly increases the surgical risk.


Asthma, allergy and bronchial hyper-reactivity to histamine in patients with bronchiectasis.
An allergy examination was made on forty-eight consecutive bronchiectasis patients, with a mean age of 37 years. Eleven had confirmed asthma and another nine, making twenty in all (42%), had distinct allergic diathesis. Allergy to a specific allergen was established in five cases. 50% of the patients in the total series had bronchial histamine hyper-reactivity, eleven without asthma or distinct allergic diathesis. The results corroborate views previously reported of the role of asthmatic symptoms and allergic diathesis as aetiological factors of bronchiectasis.


Therapeutic hypothermia in the management of acute liver failure.
A large body of experimental data and preliminary clinical studies point to the induction of mild hypothermia (32-35 °C) as a valuable approach to control the development of brain edema and intracranial hypertension in acute liver failure (ALF). The ability of hypothermia to affect multiple processes probably explains its efficacy to prevent these cerebral complications. Remarkably, mild hypothermia has been shown to prevent or attenuate most of the major alterations involved in the pathogenesis of the cerebral complications of ALF, including the accumulation of ammonia in the brain and the circulation, the alterations of brain glucose metabolism, the brain osmotic disturbances, the accumulation of glutamate and lactate in brain extracellular space, the development of inflammation and oxidative/nitrosative stress, and others. Limited information suggests that the systemic effects of hypothermia may also be beneficial for some peripheral complications of ALF. Translation of the beneficial effects of therapeutic hypothermia into standard clinical practice, however, needs to be confirmed in adequately designed clinical trials. Such trials will be important to determine the safety of therapeutic hypothermia, to identify which patients might benefit from it, and to provide the optimal guidelines for its use in patients with ALF.


Multi-frequency EIT hardware system based on DSP.
Electrical impedance tomography (EIT) is a new functional imaging technique in the biomedical engineering. A multi-frequency hardware EIT system based on digital signal processor (DSP) has been developed, and the system also has been designed using modular structure. Some experiments in vitro tissue are done and their images are generated with the filtered back-projection algorithm using this system in real time. The results show that this system is feasible, stable, convenient and extended.


Immediate and long-term effects of opiate antagonists on postictal behaviour following amygdala kindling in the rat.
Male Wistar rats implanted with bipolar electrodes in the amygdaloid complex were kindled. Subcutaneous injection of naloxone or naltrexone in low doses--0.12 and 0.24 mg/kg, respectively--dramatically reduced the postictal behavioural depression (BD) at 10 or 60 min. Remarkably, the BD was still reduced one day later. It would appear that the brain mechanisms involved in postictal BD use mu-receptors since BD is quite sensitive to low doses of the preferential antagonists naloxone and naltrexone. The long-term effects, the most novel aspect of these studies, are probably related to immediate effects but could be produced through slow genomic processes or alteration of the response to endogenously released enkephalins.


Ent-trachyloban-19-oic acid isolated from Iostephane heterophylla as a promising antibacterial agent against Streptococcus mutans biofilms.
From the roots of Iostephane heterophylla, six known compounds, namely, ent-trachyloban-19-oic acid (1), the mixture of ent-kaur-16-en-19-oic acid (2) and ent-beyer-15-en-19-oic acid (3), xanthorrhizol (4), 16α-hydroxy-ent-kaurane (5) and 16α-hydroxy-ent-kaur-11-en-19-oic acid (6) were isolated using a bioassay-guided fractionation method. The known compounds (1-6) were identified by comparison of their spectroscopic data with reported values in the literature. In an attempt to increase the resultant antimicrobial activity of 1 and 4, a series of reactions was performed on ent-trachyloban-19-oic acid (1) and xanthorrhizol (4), to obtain derivatives 1a, 1b, and 4a-4d. All the isolated compounds (1-6) and the derivatives 1a, 1b, and 4a-4d were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Porphyromonas gingivalis associated with caries and periodontal disease, respectively. Compounds 1, 1b, 2+3, 4 and 4d inhibited the growth of S. mutans with concentrations ranging from 4.1 μg/mL to 70.5 μg/mL. No significant activity was found on P. gingivalis except for 4 with an MIC of 6.8 μg/mL. The ability of 1, 1b, 2+3, 4 and 4d to inhibit biofilm formation by S. mutans was evaluated. It was found that 1, 1b, 4 and 4d interfered with the establishment of S. mutans biofilms, inhibiting their development at 32.5, 125.0, 14.1 and 24.4 μg/mL, respectively.


Canid herpesvirus 1 (CHV-1)-related disease in older puppies and CHV-1 shedding in the vagina of adult pregnant dogs.
A large breeding kennel of Bulldogs (n = 57) experienced several Canid herpesvirus 1 (CHV-1)-related diseases in older puppies (9 weeks of age) in Arkansas. CHV-1 has been repeatedly confirmed in the kennel in several animals for 3 years (January 2012-February 2015) using various virology tests. I was able to detect a partial sequence of CHV DNA (~120 bp) in archived formalin-fixed, paraffin-embedded tissue blocks after 3 years of storage. CHV-1 is persistently circulating in this kennel in spite of high serum antibody titers in the adult dogs. The dogs were negative for canine brucellosis antibodies based on Brucella canis rapid card test.


Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking.
Galectin-1 (Gal-1) is a beta-galactoside-binding protein, the expression of which is increased in endothelial cells on exposure to proinflammatory stimuli. Through binding of several receptors (CD7, CD45, and CD43) Gal-1 is known to induce apoptosis of activated T lymphocytes, an effect thought to mediate the beneficial effects it exerts in various inflammatory models. The data presented here highlights another function for Gal-1, that of a negative regulator of T-cell recruitment to the endothelium under both physiological and pathophysiological conditions. We have shown, using siRNA to knockdown Gal-1 in endothelial cells, that endogenous Gal-1 limits T-cell capture, rolling, and adhesion to activated endothelial cells under flow. Furthermore, the reverse effect is observed when exogenous human recombinant Gal-1 is added to activated endothelial monolayers whereby a dramatic reduction in lymphocyte recruitment is seen. These findings are corroborated by studies in Gal-1 null mice in which homing of wild-type (WT) T lymphocytes is significantly increased to mesenteric lymph nodes and to the inflamed paw in a model of delayed-type hypersensitivity. In conclusion, mimicking endothelial Gal-1 actions would be a novel strategy for controlling aberrant T-cell trafficking, hence for the development of innovative anti-inflammatory therapeutics.


Fibronectin induces endothelial cell migration through β1 integrin and Src-dependent phosphorylation of fibroblast growth factor receptor-1 at tyrosines 653/654 and 766.
The extracellular matrix microenvironment regulates cell phenotype and function. One mechanism by which this is achieved is the transactivation of receptor tyrosine kinases by specific matrix molecules. Here, we demonstrate that the provisional matrix protein, fibronectin (FN), activates fibroblast growth factor (FGF) receptor-1 (FGFR1) independent of FGF ligand in liver endothelial cells. FN activation of FGFR1 requires β1 integrin, as evidenced by neutralizing antibody and siRNA-based studies. Complementary genetic and pharmacologic approaches identify that the non-receptor tyrosine kinase Src is required for FN transactivation of FGFR1. Whereas FGF ligand-induced phosphorylation of FGFR1 preferentially activates ERK, FN-induced phosphorylation of FGFR1 preferentially activates AKT, indicating differential downstream signaling of FGFR1 in response to alternate stimuli. Mutation analysis of known tyrosine residues of FGFR1 reveals that tyrosine 653/654 and 766 residues are required for FN-FGFR1 activation of AKT and chemotaxis. Thus, our study mechanistically dissects a new signaling pathway by which FN achieves endothelial cell chemotaxis, demonstrates how differential phosphorylation profiles of FGFR1 can achieve alternate downstream signals, and, more broadly, highlights the diversity of mechanisms by which the extracellular matrix microenvironment regulates cell behavior through transactivation of receptor tyrosine kinases.


Protocol for the Systematic Fixation, Circuit-Based Sampling, and Qualitative and Quantitative Neuropathological Analysis of Human Brain Tissue.
Human brain tissue has long been a critical resource for neuroanatomy and neuropathology, but with the advent of advanced imaging and molecular sequencing techniques, it has become possible to use human brain tissue to study, in great detail, the structural, molecular, and even functional underpinnings of human brain disease. In the century following the first description of Alzheimer's disease (AD), numerous technological advances applied to human tissue have enabled novel diagnostic approaches using diverse physical and molecular biomarkers, and many drug therapies have been tested in clinical trials (Schachter and Davis, Dialogues Clin Neurosci 2:91-100, 2000). The methods for brain procurement and tissue stabilization have remained somewhat consistently focused on formalin fixation and freezing. Although these methods have enabled research protocols of multiple modalities, new, more advanced technologies demand improved methodologies for the procurement, characterization, stabilization, and preparation of both normal and diseased human brain tissues. Here, we describe our current protocols for the procurement and characterization of fixed brain tissue, to enable systematic and precisely targeted diagnoses, and describe the novel, quantitative molecular, and neuroanatomical studies that broadly expand the use of formalin-fixed, paraffin-embedded (FFPE) tissue that will further our understanding of the mechanisms underlying human neuropathologies.


Nursing care of Arab children: consideration of cultural factors.
As the number of Arabs living in the United States increases, so does the number of children of Arab descent seeking medical attention. However, despite the sizable and ever increasing number of American Arabs, their health beliefs and practices remain relatively unexplored. When cultural differences exist with regard to beliefs about health and illness, health practices, and health-seeking behavior, the process of health-related interaction becomes difficult and often detrimental to health outcomes. Among Arab immigrants, their children tend to be the least visible population. This article describes the beliefs and practices, both cultural and health-related, of Arab families, with an emphasis on child care and rearing. Nursing considerations, which take these cultural factors into account, are discussed that will accommodate the needs of Arab children receiving professional Western medical treatment.


Deep Neck Infection Complicated by Phlegmonous Esophagitis and Mediastinitis.
Descending necrotizing mediastinitis is a life-threatening disease that extends into the pretracheal, perivascular, retrovisceral, and/or prevertebral spaces, generally sparing the esophagus. We report a case of deep neck abscess complicated by phlegmonous esophagitis and mediastinitis. The patient was successfully treated with antibiotics and surgery, combining transcervical and bilateral thoracoscopic transthoracic mediastinal drainage. However, a pseudo-lumen with a large amount of pus remained in the esophagus. The septum between the true and the pseudo-lumen was cut endoscopically, after which the patient recovered well without any complications.


Embryo implantation after human in vitro fertilization: importance of endometrial receptivity.
To study the effects of controlled ovarian hyperstimulation (COH) on endometrial receptivity during human in vitro fertilization (IVF), we compared embryo implantation data obtained from our nonanonymous donor oocyte program with those obtained from standard IVF. To control for embryo quality, IVF patient characteristics were matched to those of the oocyte donors with regard to age and previous gravidity. All cycles were performed in an identical manner, using standardized ovarian stimulation protocols, transvaginal follicle aspiration, fertilization and culture in vitro, and transcervical embryo transfer. A similar number of oocytes per cycle were obtained, fertilization rates were similar, and similar numbers of embryos were transferred in both groups. Transferred embryos had similar numbers of blastomeres and were morphologically judged to be of similar quality in both groups. Implantation rates per individual embryo were significantly higher in donor than in standard IVF (35% versus 10.7%) as were ongoing per embryo implantation rates (23% versus 8%). Clinical and ongoing pregnancy rates per cycle were likewise higher in the donor group than in the standard IVF group (67% versus 39%, and 61% versus 30%, respectively). We conclude that COH inhibits embryo implantation after IVF by decreasing endometrial receptivity, which is an important factor in IVF pregnancy success.


Rasmussen encephalitis.
Rasmussen encephalitis (RE) is a rare, inflammatory, and possibly immuno-mediated disease that typically affects one hemisphere. The two cardinal symptoms are progressive neurological deficits and intractable seizures, often in the form of epilepsia partialis continua and recurring epileptic status. Distinctive MRI features include progressive unilateral focal cortical atrophy and gray or white matter high-signal changes with basal ganglion involvement. Histopathology is characterized by brain inflammation dominated by T cells, microglial activation, and microglial nodules, followed by neuronal loss and astrogliosis. The diagnosis of RE, which may be particularly challenging in the initial stages, is based on clinical and laboratory findings. The diagnosis requires the exclusion of other causes of epilepsia partialis continua, and other cerebral focal inflammatory diseases. The treatment of RE is often demanding: antiepileptic drugs are of limited effect, whereas the surgical exclusion of the affected hemisphere offers a very high chance of seizure freedom but at the price of irreversible neurological deficits. By contrast, long-term immunotherapy may delay hemispheric tissue loss and neurological deficits, but has a lesser effect on total seizure burden. Given that the severity of symptoms varies among different patients and phases, the therapeutic strategy, including medical and surgical options, must be tailored to the need of each patient.


Isovolumetric Relaxation Time (IVRT): An Effective Tool in Management of Subclinical Hypothyroidism.
Hypothyroidism is a common condition in which thyroid gland doesn't produce sufficient thyroid hormone. Normal range of TSH is 0.4 to 4 mIU/L. Patients with TSH between 5 and 10 mIU/L, with normal T4 are diagnosed to have subclinical hypothyroidism. Decision to treat, particularly the subclinical hypothyroidism is tailored to individual patients. In our study, isovolumetric relaxation time (IVRT) was used to detect the diastolic function of cardia in hypothyroid patient, with the help of 2D echocardiogram. Normal duration of IVRT is 54 to 65 μs and in hypothyroidism it is expected to increase. To assess, whether IVRT is an effective tool in the management of subclinical hypothyroidism. 50 patients attending otorhinolaryngology OPD with TSH level of 5 to 10 mIU/L were selected for the study. All these were sent for 2D echocardiogram, for the measurement of IVRT. These 50 patients were divided into 2 groups. Group A-patients with TSH level 5 to 10 mIU/L and normal IVRT. Group B-patients with TSH level 5 to 10 mIU/L and prolonged IVRT. Patients in Group A were not given thyroxine, and after 3 months, they were reviewed with TSH level and IVRT duration. Patients in Group B were started with thyroxine, and after 3 months, they were reviewed with TSH level and IVRT duration. The basal and 3 months follow up values of TSH and IVRT was analysed on both the groups. The p value of group A was not significant, but p value group B was significant. IVRT as a measuring tool in sub clinical hypothyroidism will definitely bring a major change in the concepts of treatment.


Optimizing cluster survey designs for estimating trachomatous inflammation-follicular within trachoma control programs.
The World Health Organization recommends mass drug administration (MDA) with azithromycin to eliminate trachoma as a public health problem. MDA decisions are based on prevalence estimates from two-stage cluster surveys. There is a need to mathematically evaluate current trachoma survey designs. Our study aimed to characterize the effects of the number of units sampled on the precision and cost of trachomatous inflammation-follicular (TF) estimates. A population of 30 districts was simulated to represent the breadth of possible TF distributions in Amhara, Ethiopia. Samples of varying numbers of clusters (14-34) and households (10-60) were selected. Sampling schemes were evaluated based on precision, proportion of incorrect and low MDA decisions made, and estimated cost. The number of clusters sampled had a greater impact on precision than the number of households. The most efficient scheme depended on the underlying TF prevalence in a district. For lower prevalence areas (< 10%) the most cost-efficient design (providing adequate precision while minimizing cost) was 20 clusters of 20-30 households. For higher prevalence areas (> 10%), the most efficient design was 15-20 clusters of 20-30 households. For longer-running programs, using context-specific survey designs would allow for practical precision while reducing survey costs. Sampling 15 clusters of 20-30 households in suspected moderate-to-high prevalence districts and 20 clusters of 20-30 households in districts suspected to be near the 5% threshold appears to be a balanced approach.


The in vivo effect of bilirubin and sulfisoxazole on cerebral oxygen, glucose, and lactate metabolism in newborn piglets.
Bilirubin inhibits in vitro oxidative phosphorylation and glycolysis. This study investigated the in vivo effect of bilirubin on cerebral oxygen, glucose, and lactate uptake in newborn piglets. Seventeen 2- to 4-day-old piglets were divided into three groups and examined as follows: group 1 = control (C); group 2 = control with sulfisoxazole; and group 3 = experimental, given bilirubin with sulfisoxazole. In the experimental group, bilirubin was infused for 4 h. The cerebral bilirubin content in the bilirubin-infused group was 11.0 +/- 1.4 nmol/g of cerebral cortex (mean +/- SEM), consistent with levels found in infants with kernicterus. However, this level of brain bilirubin had no major, acute effects on cerebral uptake of oxygen, glucose, or lactate despite producing lethargy and ataxia which were consistent with bilirubin intoxication. This suggests that mitochondrial changes may not be involved in vivo in acute bilirubin encephalopathy.


Frictional response of articular cartilage containing crystals.
Many joint diseases are associated with the deposition of crystals in articular cartilage. Three main types are commonly found: calcium pyrophosphate, calcium hydroxyapatite and monosodium urate. The effects of these articular crystals on the frictional properties and the surface condition of the articular cartilage were studied. A total of 43 cartilage specimens cut from 19 post-mortem knee joints have been tested in purpose-designed apparatus. The results show that a high friction coefficient and a high level of crystal deposition tend to occur with a worsening of the surface quality of the articular cartilage.


TEOS: A framework for constructing operational definitions of medication adherence based on Timelines-Events-Objectives-Sources.
Managing adherence to medications is a priority for health systems worldwide. Adherence research is accumulating, yet the quality of the evidence is reduced by various methodological limitations. In particular, the heterogeneity and low accuracy of adherence measures have been highlighted in many literature reviews. Recent consensus-based guidelines advise on best practices in defining adherence (ABC) and reporting of empirical studies (EMERGE). While these guidelines highlight the importance of operational definitions in adherence measurement, such definitions are rarely included in study reports. To support researchers in their measurement decisions, we developed a structured approach to formulate operational definitions of adherence. A group of adherence and research methodology experts used theoretical, methodological and practical considerations to examine the process of applying adherence definitions to various research settings, questions and data sources. Consensus was reached through iterative review of discussion summaries and framework versions. We introduce TEOS, a four-component framework to guide the operationalization of adherence concepts: (1) describe treatment as four simultaneous interdependent timelines (recommended and actual use, conditional on prescribing and dispensing); (2) locate four key events along these timelines to delimit the three ABC phases (first and last recommended use, first and last actual use); (3) revisit study objectives and design to fine-tune research questions and assess measurement validity and reliability needs, and (4) select data sources (e.g., electronic monitoring, self-report, electronic healthcare databases) that best address measurement needs. Using the TEOS framework when designing research and reporting explicitly on these components can improve measurement quality.


Optimal multiresolution 3D level-set method for liver segmentation incorporating local curvature constraints.
Advanced liver surgery requires a precise pre-operative planning, where liver segmentation and remnant liver volume are key elements to avoid post-operative liver failure. In that context, level-set algorithms have achieved better results than others, especially with altered liver parenchyma or in cases with previous surgery. In order to improve functional liver parenchyma volume measurements, in this work we propose two strategies to enhance previous level-set algorithms: an optimal multi-resolution strategy with fine details correction and adaptive curvature, as well as an additional semiautomatic step imposing local curvature constraints. Results show more accurate segmentations, especially in elongated structures, detecting internal lesions and avoiding leakages to close structures.


Parallelism Between Sentence Structure and Nominal Phrases in Japanese: Evidence from Scrambled Instrumental and Locative Adverbial Phrases.
The present study investigated the canonical position of instrumental and locative adverbial phrases in both Japanese sentences and noun phrases to determine whether the canonical positions are parallel. A series of sentence/phrase decision tasks were used to compare sentences with different word-orders, including sentences with SAdvOV (S is subject phrase, Adv adverb, O object phrase and V verb), AdvSOV, SAdvOV and SOAdvV word orders. SAdvOV word order was found to be the most quickly processed, for both instrumental adverbial (Experiment 1) and locative adverbial phrases (Experiment 2). Thus, the canonical position for these adverbial phrases is identified as the position immediately preceding the object (Theme argument). This finding was replicated when the same experimental methods were applied to event-denoting noun phrases. Adverbial adjuncts in the initial position (AdvON, N is noun phrase) were processed more quickly and accurately than noun phrases with adverbial phrases in the second position (OAdvN), for both instrumental adverbial (Experiment 3) and locative adverbial phrases (Experiment 4). Therefore, the position immediately preceding the object is the canonical position for both instrumental and locative adverbial phrases in sentences and in noun phrases. In conclusion, this indicates that the base structure of a sentence is shared by its related noun phrase.


Differential release of vasopressin and oxytocin in response to abdominal vagal afferent stimulation or apomorphine in the ferret.
The aim of this study was to investigate whether direct afferent stimulation of the abdominal vagus could promote release of the neurohypophyseal hormones. The nucleus of the solitary tract is the major recipient of vagal afferent information, and this region of the brainstem may also be activated by stimulation of the area postrema. For this reason apomorphine, a D2 dopaminergic agonist which acts on the area postrema, and can evoke vasopressin secretion in man, was also investigated for its effect on vasopressin and oxytocin release. Our results show that vasopressin, but not oxytocin is released in vast amounts in response to electrical afferent stimulation of the abdominal vagus. Administration of apomorphine also evoked a massive vasopressin release with less marked effects on oxytocin. The possible functional implications of these results are discussed especially in the context of nausea and vomiting.


Transrectal Saturation Biopsy Improves Risk Stratification (Reclassification) of Patients with Prostate Cancer on Active Surveillance.
We assessed the accuracy of transrectal saturation prostate biopsy compared to extended prostate biopsy in patients on active surveillance. Determining prostate cancer aggressiveness is mandatory to determine appropriate candidates for active surveillance and appropriateness to remain on active surveillance protocols. From our institutional review board approved database we reviewed the biopsies of 277 patients diagnosed with prostate cancer on an active surveillance protocol. Eligibility criteria included clinical stage T1 to T2a, Gleason score 6 or less, prostate specific antigen 10 ng/ml or less and percent of positive cores 33% or less of the total cores taken on diagnostic biopsy. We defined recategorization or pathological progression on first confirmatory and surveillance biopsies as no longer meeting the standard definition of low risk by cancer volume or Gleason score criteria. Of 444 biopsies 279 were extended prostate biopsy (10 to 14 cores) and 165 were saturation prostate biopsy (20 cores or greater). The rate of cancer recategorization (reclassification) was highest on the first confirmatory biopsy at 25%. There was no significant difference between extended and saturation prostate biopsy for detecting recategorization on the first confirmatory biopsy (21.5% vs 29.4%, p = 0.13). Saturation prostate biopsy was significantly more likely to detect cancer progression on all subsequent surveillance biopsies. Disease progression or recategorization was more frequently identified on the first confirmatory biopsy than on subsequent surveillance biopsies. The incidence of disease recategorization was higher in the saturation biopsy group than in the extended biopsy group on the first confirmatory biopsy but the difference was not statistically significant. Disease progression was more likely to be identified by saturation prostate biopsy on subsequent surveillance biopsies.


X-ray tube with artificial neural network model as a promising alternative for radioisotope source in radiation based two phase flowmeters.
In this paper, X-ray tube is introduced as a potential alternative for radioisotope sources used in radiation based liquid-gas two-phase flowmeters. X-ray tubes have lots of advantages over the radioisotope sources such as having an adjustable emitting photon's energy, being safer from point of view of radiation health physics during the transportation of the source, having ability to generate a high flux photon beam, and etc. The proposed radiation based system in this study composes an X-ray tube with a tube voltage of 150 kV and a 2.5 mm aluminum filter as the radiation source and one sodium iodide crystal as the photon detector. A pipe was positioned between the X-ray tube and the detector. Two main flow regimes of annular and stratified with different void fractions were modelled inside the pipe. Artificial neural network model of multi-layer perceptron (MLP) was also used in this study for analyzing the obtained data. The output spectrum of sodium iodide detector with 150 samples was applied as the input of multi-layer perceptron network and void fraction was considered as its output. The root mean squared error of proposed measuring system was 4.13 which shows the X-ray tube can be implemented as a promising alternative for radioisotope in radiation based two phase flow meters.


Assessing new bone formation in neonatal calvarial organ cultures.
Bone formation is a complex process, and testing anabolic effects on the skeleton of agents is slow and expensive in animals. Neonatal mouse calvariae cultured ex vivo show strong anabolic or catabolic bone responses to 1-week treatments and can be analyzed by quantitative histomorphometry. Changes in new bone area and osteoblast number caused by added proteins, drugs, or transfected genes can be quantified and analyzed for statistical significance. The organ cultures preserve much of the skeletal architecture and cellular diversity present in vivo and offer greater physiological relevance than cell lines studied in vitro.


Synthesis and biological activity of novel thiazolidinediones.
Novel compounds having a dual pharmacophore were synthesised and evaluated for their insulin sensitiser and anti-inflammatory properties in different animal models.


Odyssey of a sailor's diagnosis since 1795 AD.
In the year 1795, a British East Indiaman bound for China had a sick sailor on board who was diagnosed as having testis cancer by the ship's surgeon, who then treated him with an antiscorbutic diet, because scurvy was rampant among the sailors. He was completely cured of his cancer, as reported in the Edinburgh Medical and Surgical Journal by Livingstone in 1805. However, the sailor actually had scurvy and not testis cancer. This diagnostic error has been perpetuated in the medical literature until rectified by Shetty after 191 years. This is reconstructed account of the sailor's case history and the ship's journey as it actually took place in 1795 AD.


Pair-dependent co-aggregation behavior of non-flocculating sludge bacteria.
Two strains of non-flocculating sewage sludge bacteria (Xanthomonas sp. S53 and Microbacterium esteraromaticum S51) showed 91% and 77% co-aggregation, respectively, with Acinetobacter johnsonii S35 using a spectrophometric assay. The co-aggregates in case of Xanthomonas sp. S53 and A. johnsonii S35 were above 100 microm and stable against EDTA (2 mM) and a commercial protease (0.2 mg ml(-1)). Protease/periodate pretreatment of the partners did not affect this co-aggregation. On the other hand, co-aggregates of M. esteraromaticum S51 and A. johnsonii S35 (50-70 microm) were deflocculated by EDTA or protease. Protease pretreatment of M. esteraromaticum S51 and periodate pretreatment of A. johnsonii S35 prevented their co-aggregation with respective untreated partners. The potential co-aggregation mechanisms of A. johnsonii S35 varied depending upon the other partner involved.


Parkinson Disease: The Relationship Between Non-motor Symptoms and Motor Phenotype.
Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothesized that the PIGD phenotype would be more likely to develop NMS, and that the non-dopamine-responsive axial signs would correlate with NMS severity. We conducted a retrospective cross-sectional chart review to assess the relationship between NMS and PD motor phenotypes. PD patients were administered the NMS Questionnaire, the UPDRS-III, and the Mini-Mental State Examination score. The relationship between NMS burden and PD subtypes was examined using linear regression models. The prevalence of each NMS among difference PD motor subtypes was analyzed using chi-square test. PD patients with more advanced disease based on their UPDRS-III had higher NMS Questionnaire scores. The axial component of UPDRS-III correlated with higher NMS. There was no correlation between NMS and tremor scores. There was a significant correlation between PIGD score and higher NMS burden. PIGD group had higher prevalence in most NMS domains when compared with tremor dominant and indeterminate groups independent of disease duration and severity. NMS profile and severity vary according to motor phenotype. We conclude that in the PD population, patients with a PIGD phenotype who have more axial involvement, associated with advanced disease and poor motor response, have a higher risk for a higher NMS burden.


A review: application of remote sensing as a promising strategy for insect pests and diseases management.
The present review provides a perspective angle on the historical and cutting-edge strategies of remote sensing techniques and its applications, especially for insect pest and plant disease management. Remote sensing depends on measuring, recording, and processing the electromagnetic radiation reflected and emitted from the ground target. Remote sensing applications depend on the spectral behavior of living organisms. Today, remote sensing is used as an effective tool for the detection, forecasting, and management of insect pests and plant diseases on different fruit orchards and crops. The main objectives of these applications were to collate data that help in decision-making for insect pest management and decreasing the environmental pollution of chemical pesticides. Airborne remote sensing has been a promising and useful tool for insect pest management and weed detection. Furthermore, remote sensing using satellite information proved to be a promising tool in forecasting and monitoring the distribution of locust species. It has also been used to help farmers in the early detection of mite infestation in cotton fields using multi-spectral systems, which depend on color changes in canopy semblance over time. Remote sensing can provide fast and accurate forecasting of targeted insect pests and subsequently minimizing pest damage and the management costs.


Identification of raloxifene as a novel CB2 inverse agonist.
The purpose of the current study was to apply a high throughput assay to systematically screen a library of food and drug administration (FDA)-approved drugs as potential ligands for the cannabinoid receptor 2 (CB2). A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring changes in intracellular cAMP levels was validated and found to be suitable for testing ligands that may act on CB2. Among the 640 FDA-approved drugs screened, raloxifene, a drug used to treat/prevent post-menopausal osteoporosis, was identified for the first time to be a novel CB2 inverse agonist. Our results demonstrated that by acting on CB2, raloxifene enhances forskolin-stimulated cAMP accumulation in a concentration-dependant manner. Furthermore, our data showed that raloxifene competes concentration-dependently for specific [(3)H]CP-55,940 binding to CB2. In addition, raloxifene pretreatment caused a rightward shift of the concentration-response curves of the cannabinoid agonists CP-55,940, HU-210, and WIN55,212-2. Raloxifene antagonism is most likely competitive in nature, as these rightward shifts were parallel and were not associated with any changes in the efficacy of cannabinoid agonists on CB2. Our discovery that raloxfiene is an inverse agonist for CB2 suggests that it might be possible to repurpose this FDA-approved drug for novel therapeutic indications for which CB2 is a target. Furthermore, identifying raloxifene as a CB2 inverse agonist also provides important novel mechanisms of actions to explain the known therapeutic effects of raloxifene.


A comparison of metabolic health parameters in ICSI-conceived and naturally conceived adolescents.
Are there differences in the cardiometabolic health of ICSI-conceived adolescents compared with a control group, taking parental risk factors into account? ICSI-conceived adolescents (n = 272), their mothers (n = 273) and naturally conceived control adolescents (n = 273) and their mothers (n = 273) provided a blood test and answered a health-related questionnaire. The adolescents also attended a physical examination. ICSI-conceived males showed significantly higher mean weight (72.6 ± 15.1 versus 67.7 ± 12.6 kg, P = 0.005), body mass index (BMI) (22.2 ± 3.7 versus 21.0 ± 3.2 kg/m2, P = 0.007) and waist circumference (79.1 ± 11.6 versus 74.5 ± 8.7 cm, P < 0.001). The mean values for weight and BMI were also significantly higher in the ICSI parents. In the ICSI-conceived females significant differences in high-density lipoprotein cholesterol (1.5 ± 0.3 versus 1.6 ± 0.3 mmol/l, P = 0.033) and triglyceride values (1.1 ± 0.5 versus 1.0 ± 0.4 mmol/l, P = 0.013) were observed. ICSI mothers also had significantly higher triglycerides (P = 0.002), higher glutamate pyruvate transaminase/alanine aminotransferase (P < 0.001) and higher alkaline phosphatase values (P < 0.001). Increased values for weight were found in the male and differences in lipid parameters in the female ICSI-conceived adolescents, which were reflected in the values of their parents. Adjustment for parental risk factors generally attenuated the differences between the ICSI and the control groups, but did not completely remove them. Whether these observed differences are clinically relevant for the future health of the participants requires further study. To increase knowledge in this area, future studies should also include parental data.


Degenerative Scoliosis.
The purpose of this review is to provide an updated review of adult degenerative scoliosis (ADS). Epidemiology, classification, pathophysiology, and natural history are discussed along with a summary of commonly used outcome measures. Operative vs non-operative outcomes and new surgical techniques are discussed. The SRS-Schwab classification (2012) combines clinical and radiographic evaluation including overall global alignment. Current evidence regarding risk factors and efficacy of non-surgical modalities are discussed. Recent studies have reported surgical management to provide superior outcomes to non-operative modalities. New surgical techniques provide promising early data in regard to decreasing perioperative morbidity. ADS is a potentially debilitating condition that occurs with asymmetric spinal degeneration. This can produce global sagittal malalignment and central and foraminal stenosis and can lead to significant impairment often necessitating surgery. The surgeon must be aware of the perioperative risks in this population and implement appropriate age-specific alignment goals to achieve the best outcome for patients.


Planar Spin Glass with Topologically Protected Mazes in the Liquid Crystal Targeting for Reconfigurable Micro Security Media.
The planar spin glass pattern is widely known for its inherent randomness, resulting from the geometrical frustration. As such, developing physical unclonable functions (PUFs)-which operate with device randomness-with planar spin glass patterns is a promising candidate for an advanced security systems in the upcoming digitalized society. Despite their inherent randomness, traditional magnetic spin glass patterns pose considerable obstacles in detection, making it challenging to achieve authentication in security systems. This necessitates the development of facilely observable mimetic patterns with similar randomness to overcome these challenges. Here, a straightforward approach is introduced using a topologically protected maze pattern in the chiral liquid crystals (LCs). This maze exhibits a comparable level of randomness to magnetic spin glass and can be reliably identified through the combination of optical microscopy with machine learning-based object detection techniques. The "information" embedded in the maze can be reconstructed through thermal phase transitions of the LCs in tens of seconds. Furthermore, incorporating various elements can enhance the optical PUF, resulting in a multi-factor security medium. It is expected that this security medium, based on microscopically controlled and macroscopically uncontrolled topologically protected structures, may be utilized as a next-generation security system.


Primary jejunal malignant melanoma first noticed because of the presence of parotid lymph node metastasis.
The case of a 71-year-old Japanese man with primary jejunal melanoma with an unusual clinical course is reported. Several cases of primary malignant melanoma of the small intestine have been reported, but in most cases no clear evidence has shown whether the lesions were primary or metastatic. We discuss why the tumor in our case was considered primary, and we review similar cases of primary melanoma of the small intestine.


Topsoil application during the rehabilitation of a manganese tailing dam increases plant taxonomic, phylogenetic and functional diversity.
Rehabilitation of tailing dams poses important challenges because sterile materials and poor or even toxic soils hinder plant development and the regeneration of the pre-mining-activity biota. In this study, we analyzed the effectiveness of rehabilitating a 14-year-old manganese tailing dam by comparing three different regeneration treatments (topsoil application, seedling plantation and spontaneous regeneration) with undisturbed reference sites. We used soil chemical composition, taxonomic, functional and phylogenetic diversity and the above-ground tree biomass as indicators of rehabilitation success. In terms of soil chemical composition, we showed that the seedling and natural regeneration treatments were similar to one another but different from the reference sites. Topsoil application presented an intermediate chemical composition between the reference site and the other two treatments. Moreover, the species richness, Shannon diversity index and phylogenetic diversity indicated faster rehabilitation of ecosystem biodiversity with the topsoil treatment, although levels from reference are not yet achieved. We also observed higher basal area and biomass production in the topsoil treatment. However, these patterns were not observed for functional diversity, for which no differences among treatments were observed. We concluded that topsoil application provided the best results; however, we must emphasize that even this approach was not sufficient to rehabilitate the system to the similar level of biodiversity found in the surrounding ecosystem up to the present.


Borrelia-infection rates in tick and insect vectors accompanying human risk of acquiring Lyme borreliosis in a highly endemic region in Central Europe.
The methods of spatial statistics were applied to assess the geographical pattern of risk of Lyme borreliosis in Central Bohemia, the Czech Republic, based on retrospective data on disease contractions. The statistical risk was then compared at 15 selected localities with the infection challenge presented by ticks and insects carrying borreliae. Over 5,000 Ixodes ricinus (L.) ticks and 390 haematophagous dipterans were screened by direct immunofluorescence method, and the spatial and seasonal variance of infection rates were studied. Infected ticks were found at each locality throughout the warm season; in nymphs, sample infection rates ranged from 4.9% to 23.1% with a mean of 14.5% in spring, from 7.7% to 28.7% with a mean of 16.1% in summer, and from 7% to 20.6% with a mean of 13.6% in autumn. The statistical risk was found to correlate well with an average nymphal infection challenge, i.e. I. ricinus nymphal abundance x infection rate, at a given locality. Statistically significant cumulation of insect-history recalling patients into several, generally wetland, areas was ascertained; borreliae were revealed in 0.5% of the dipterans examined.


Congenital membrane causing duodenal obstruction and malpositioning of the descending colon.
A congenital membrane without intestinal malrotation is a rare cause of duodenal obstruction. Here we present an 11-year-old girl who had suffered from intermittent abdominal cramping pain and vomiting for more than 5 years. The image studies, including a plain abdomen roentgenogram and sonogram, showed no definite diagnosis. The upper gastrointestinal series and small bowel series showed the contrast was static over the third portion of the duodenum and the descending colon pulled up toward the epigastric area. Laparoscopic exploration revealed a congenital membrane extending from the right-side paraduodenal peritoneum through the third portion of the duodenum to the descending colon, which had caused obstruction of the third portion of the duodenum and malpositioning of the descending colon. To the best of our knowledge, this is the first case report in the literature where a congenital membrane caused both duodenal obstruction and malpositioning of the descending colon.


Self-reported competence, attitude and approach of physicians towards patients with dementia in ambulatory care: results of a postal survey.
Caring for patients with dementia is a demanding task. Little is known as to whether physicians feel competent enough to perform this task or whether a lack of self-perceived competence influences attitudes and professional approach. Even less is known with respect to potential differences between general practitioners (GPs) and specialists. The purpose of this study was to investigate the interrelationship between the self-perceived competence, attitude and professional approach of physicians in ambulatory care in Germany. A further aim was to compare GPs and specialists with regard to differences in these areas. A standardised postal survey was sent to 389 GPs and 239 neurologists and psychiatrists in six metropolitan areas in Germany. The 49-item questionnaire consisted of attitudinal statements to be rated on a Likert-type scale. Return rates were 54 percent for GPs and 40 percent for specialists. Statistical methods used to analyze data included correlation analysis, cluster analysis and ordinal regression analysis. No differences were found between GPs and specialists with regard to their general attitude towards caring for patients with dementia. Approximately 15 percent of both disciplines showed a clearly negative attitude. Self-reported competence was strongly associated with general attitude. In particular among GPs, and less so among specialists, a strong positive association was found between self-reported competence, general attitude and professional approach (e.g. early detection, active case finding and cooperation with caregivers). Differences between GPs and specialists were smaller than expected and appear to predominantly reflect task differences within the German health care system. Training opportunities which enable in particular GPs to enhance not only their competence but also their general attitude towards dementia care would appear to be beneficial and might carry positive consequences for patients and their caregivers.


Treatment of depression in cancer patients is associated with better life adaptation: a pilot study.
Major depression occurs in a significant number of cancer patients, and there is evidence that cancer patients with depression do not receive adequate antidepressant treatment. In an uncontrolled pilot study, the authors assess the degree of depression and the quality of life after the initiation of antidepressant medication treatment in 12 depressed cancer patients who received adequate antidepressant drugs and in 10 depressed cancer patients who received inadequate antidepressant treatment. These preliminary findings suggest that cancer patients with major depression benefit from antidepressant medication treatment and may experience an improved psychosocial adjustment to cancer. Controlled clinical trials will be necessary to verify these preliminary findings.


Follicular development and oocyte maturation after stimulation with gonadotropins versus leuprolide acetate/gonadotropins during in vitro fertilization.
Follicular development and oocyte maturation were compared in 22 patients stimulated with human menopausal gonadotropins/human chorionic gonadotropin (hCG, group I) and in 52 women also treated with the gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate (LA, group II). Suppression of endogenous leutinizing hormone (LH) surges by LA allowed delayed hCG administration, resulting in higher peripheral estradiol levels, more retrieved oocyte cumulus corona complexes, and greater numbers of cryopreserved embryos. Reduction in spontaneous LH surges in the GnRH-a cycles may have allowed time for larger follicular fluid (FF) volume accumulation during all phases of oocyte cumulus corona complex maturation, restoring synchrony between FF volume and oocyte cumulus corona complex maturity.


Changes in methane emission, rumen fermentation in response to diet and microbial interactions.
To evaluate relative contributions of different microbial groups in rumen, the mono-culture (i.e. bacteria, protozoa and fungi) and co-cultures (i.e. bacterial-protozoal, fungal-protozoal and bacterial-fungal) were tested in vitro using high and low roughage diets. Total gas and methane were higher in bacterial-fungal and bacterial-protozoal co-cultures, while lower in fungal-protozoal than controls (high and low roughage with complete rumen consortia; control 1 and 2, respectively). Digestibility and total volatile fatty acids were lower in bacterial-fungal co-culture with both high and low roughage diets. Methanogens decreased in bacterial-fungal co-culture with high roughage. With high roughage, counts were lower for bacteria with bacterial-protozoal, protozoa with fungal-protozoal, and fungi with the bacterial-fungal co-cultures. Total gas was higher in bacterial mono-culture with low roughage, but methane was not detected in any mono-culture. Digestibility and total volatile fatty acids were significantly lowered with protozoal mono-culture. Methanogens reduced significantly in mono-cultures with high roughage diet than control 1. Defaunation reduced methanogens without significantly affecting rumen fermentation.


Hemispheric specialization for visual words is shaped by attention to sublexical units during initial learning.
Selective attention to grapheme-phoneme mappings during learning can impact the circuitry subsequently recruited during reading. Here we trained literate adults to read two novel scripts of glyph words containing embedded letters under different instructions. For one script, learners linked each embedded letter to its corresponding sound within the word (grapheme-phoneme focus); for the other, decoding was prevented so entire words had to be memorized. Post-training, ERPs were recorded during a reading task on the trained words within each condition and on untrained but decodable (transfer) words. Within this condition, reaction-time patterns suggested both trained and transfer words were accessed via sublexical units, yet a left-lateralized, late ERP response showed an enhanced left lateralization for transfer words relative to trained words, potentially reflecting effortful decoding. Collectively, these findings show that selective attention to grapheme-phoneme mappings during learning drives the lateralization of circuitry that supports later word recognition. This study thus provides a model example of how different instructional approaches to the same material may impact changes in brain circuitry.


Pharmacological modulation of cortisol secretion and dexamethasone suppression in Alzheimer's disease.
We have investigated the dexamethasone suppression of cortisol release in a group of 28 patients with senile dementia of the Alzheimer type (SDAT) after stimulation by physostigmine and clonidine, as compared with basal conditions. All patients but one had previously been evaluated with a depression symptom checklist and had submitted to a standard Dexamethasone Suppression Test (DST). SDAT patients showed normal baseline cortisol values measured at 4:00 PM. DST was reproducible, but nonsuppression did not appear to be a feature of the disease, nor of the dementia syndrome, although a majority of the most demented patients were found to be nonsuppressors. Physostigmine stimulated cortisol secretion in 20 of 24 cases, irrespective of the severity of dementia. Clonidine induced a secretion in 12 of 15 cases, but this was less than that observed after cholinergic stimulation. Physostigmine made cortisol release significantly less sensitive to the suppressive effect of dexamethasone than clonidine in SDAT. This double response should be tested as a possible predictor of a cholinergic therapeutic effect.


Rheumatoid arthritis.
Management should help relieve symptoms, increase or maintain function, produce few side effects and keep the cost to a minimum. Aspirin remains the first-line drug; other nonsteroidal anti-inflammatory drugs may be useful when aspirin cannot be tolerated. Symptoms and signs of rheumatoid disease may be suppressed by corticosteroids, but only gold compounds, penicillamine and cytotoxic therapy have been shown to decrease disease activity and lessen permanent joint damage.


Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 3: A novel mechanism for the inhibition of biological membrane lipid peroxidation by dioxygenated 4-methylcoumarins mediated by the formation of a stable ADP-Fe-inhibitor mixed ligand complex.
7,8-Dihydroxy-4-methylcoumarin (DHMC) and 7,8-diacetoxy-4-methylcoumarin (DAMC) have been reported to effectively inhibit in-vivo lipid peroxidation in rat tissues induced by CCl4 and paraquat. DHMC was found to readily impart green colour to the lipid peroxidation incubation mixture containing ADP and Fe3+, whereas DAMC formed green complex only upon incubation with liver microsomes, confirming our earlier observation that liver microsomal deacetylase hydrolyses DAMC to DHMC. Sensitive pH metric technique revealed the formation of ADP-Fe-DHMC ternary complex with highest stability, while Fe-DHMC and ADP-DHMC had negligible stabilities concluding that ADP-perferryl ion formation is prevented by DHMC resulting in the production of stable ternary mixed ligand complex (ADP-Fe-DHMC), thereby inhibiting the formation of O2-, and eventually other reactive oxygen species (ROS) responsible for membrane lipid peroxidation.


Cytogenetic effects of replicating and nonreplicating strains of influenza virus on male germ cells of mice.
Evidence is presented to demonstrate that replicating (A2 and B) and nonreplicating (C) strains of influenza virus were capable of inducing higher percentages of chromosomes anomalies in spermatocytes of mice inoculated either IP or IN than were seen in controls.


Calcium is essential for fructan synthesis induction mediated by sucrose in wheat.
The role of Ca(2+) in the induction of enzymes involved in fructan synthesis (FSS) mediated by sucrose was studied in wheat (Triticum aestivum). Increase of FSS enzyme activity and induction of the expression of their coding genes by sucrose were inhibited in leaf blades treated with chelating agents (EDTA, EGTA and BAPTA). Ca(2+) channel blockers (lanthanum chloride and ruthenium red) also inhibited the FSS response to sucrose, suggesting the participation of Ca(2+) from both extra- and intra- cellular stores. Sucrose induced a rapid Ca(2+) influx into the cytosol in wheat leaf and root tissues, shown with the Ca(2+ )sensitive fluorescent probe Fluo-3/AM ester. Our results support the hypothesis that calcium is a component of the sucrose signaling pathway that leads to the induction of fructan synthesis.


Development of transgenic fish for ornamental and bioreactor by strong expression of fluorescent proteins in the skeletal muscle.
In the present study, new applications of the transgenic technology in developing novel varieties of ornamental fish and bioreactor fish were explored in a model fish, the zebrafish (Danio rerio). Three "living color" fluorescent proteins, green fluorescent protein (GFP), yellow fluorescent protein (YFP), and red fluorescent protein (RFP or dsRed), were expressed under a strong muscle-specific mylz2 promoter in stable lines of transgenic zebrafish. These transgenic zebrafish display vivid fluorescent colors (green, red, yellow, or orange) visible to unaided eyes under both daylight and ultraviolet light in the dark. The level of foreign protein expression is estimated between 3% and 17% of total muscle proteins, equivalent to 4.8-27.2mg/g wet muscle tissue. Thus, the fish muscle may be explored as another useful bioreactor system for production of recombinant proteins. In spite of the high level of foreign protein expression, the expression of endogenous mylz2 mRNAs was not negatively affected. Furthermore, compared to the wild-type fish, these fluorescent transgenic fish have no advantage in survival and reproduction.


Conversion Between the Mini-Mental State Examination and the Montreal Cognitive Assessment for Patients With Different Forms of Dementia.
The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are 2 frequently used brief cognitive screening tasks. Here, we provide a conversion method from MMSE to MoCA for patients with Alzheimer's dementia, frontotemporal dementia, and Parkinson dementia/Lewy body dementia, as well as for patients with dementia and with or without previous stroke. This conversion is needed as everyday clinical practice varies in their use of the 2 scales, which makes comparisons between studies, meta-analysis, and patient cohorts difficult. Observational cohort study. A total of 387 patients with recently diagnosed dementia in memory clinics from the Swedish registry for cognitive/dementia disorders (SveDem) from 2007 to 2018. Overall, 387 patients of the Swedish registry for cognitive/dementia disorders with both MMSE and MoCA scores were evaluated. An equipercentile equating method was used to convert MMSE to MoCA scores in the different patient populations. Furthermore, receiver operating curves were used to examine whether MMSE or MoCA scores can distinguish between patients with different dementia types. MMSE scores were converted to MoCA scores for all dementia types and depicted in a conversion table. Results show that the equipercentile equating method and log-linear smoothing allow the creation of a conversion table in which for each test score of the MMSE, the equivalent score of the MoCA for each investigated group can be looked up (and vice-versa). This study reports a reliable and easy conversion for transforming MMSE to MoCA scores (and vice-versa) in patients with Alzheimer's dementia, frontotemporal dementia, Parkinson dementia or Lewy body dementia, as well as patients with dementia with and without previous stroke.


Effect of Selective Personality-Targeted Alcohol Use Prevention on 7-Year Alcohol-Related Outcomes Among High-risk Adolescents: A Secondary Analysis of a Cluster Randomized Clinical Trial.
Alcohol consumption is one of the leading preventable causes of burden of disease worldwide. Selective prevention of alcohol use can be effective in delaying the uptake and reducing harmful use of alcohol during the school years; however, little is known about the durability of these effects across the significant transition from early adolescence into late adolescence and early adulthood. To examine the sustained effects of a selective personality-targeted alcohol use prevention program on alcohol outcomes among adolescents who report high levels of 1 of 4 personality traits associated with substance use. A cluster randomized clinical trial was conducted to assess the effectiveness of the selective personality-targeted PreVenture program on reducing the growth of risky alcohol use and related harms from early to late adolescence and early adulthood. Participants included grade 8 students attending 14 secondary schools across New South Wales and Victoria, Australia, in 2012 who screened as having high levels of anxiety sensitivity, negative thinking, impulsivity, and/or sensation seeking. Schools were block randomized to either the PreVenture group (7 schools) or the control group (7 schools). The primary end point of the original trial was 2 years post baseline; the present study extends the follow-up period from July 1, 2017, to December 1, 2019, 7 years post baseline. Data were analyzed from July 22, 2021, to August 2, 2022. The PreVenture program is a 2-session, personality-targeted intervention designed to upskill adolescents to better cope with their emotions and behaviors. Self-reported monthly binge drinking, alcohol-related harms, and hazardous alcohol use measured by the Alcohol Use Disorders Identification Test-Concise consumption screener. Of 438 participants (249 male [56.8%]; mean [SD] age, 13.4 [0.5] years) from 14 schools, 377 (86.2%) provided follow-up data on at least 2 occasions, and among those eligible, 216 (54.0%) participated in the long-term follow-up. Compared with the control condition, the PreVenture intervention was associated with reduced odds of any alcohol-related harm (odds ratio [OR], 0.81 [95% CI, 0.70-0.94]) and a greater mean reduction in the frequency of alcohol-related harms (β = -0.22 [95% CI, -0.44 to -0.003]) at the 7.0-year follow-up. There were no differences in the odds of monthly binge drinking (OR, 0.80 [95% CI, 0.56-1.13]) or hazardous alcohol use (OR, 0.87 [95% CI, 0.59-1.27]) at the 7.0-year follow-up. Exploratory analyses at the 5.5-year follow-up showed that compared with the control condition, the PreVenture intervention was also associated with reduced odds of monthly binge drinking (OR, 0.87, [95% CI, 0.77-0.99]) and hazardous alcohol use (OR, 0.91 [95% CI, 0.84-0.99]), but this was not sustained. This study demonstrated that a brief selective personality-targeted alcohol use prevention intervention delivered in the middle school years can have sustained effects into early adulthood. anzctr.org.au Identifier: ACTRN12612000026820.


Sarcomere length dependent effects on the interaction between cTnC and cTnI in skinned papillary muscle strips.
Sarcomere length dependent activation (LDA) of myocardial force development is the cellular basis underlying the Frank-Starling law of the heart, but it is still elusive how the sarcomeres detect the length changes and convert them into altered activation of thin filament. In this study we investigated how the C-domain of cardiac troponin I (cTnI) functionally and structurally responds to the comprehensive effects of the Ca(2+), crossbridge, and sarcomere length of chemically skinned myocardial preparations. Using our in situ technique which allows for simultaneous measurements of time-resolved FRET and mechanical force of the skinned myocardial preparations, we measured changes in the FRET distance between cTnI(167C) and cTnC(89C), labeled with FRET donor and acceptor, respectively, as a function of [Ca(2+)], crossbridge state and sarcomere length of the skinned muscle preparations. Our results show that [Ca(2+)], cross-bridge feedback and sarcomere length have different effects on the structural transition of the C-domain cTnI. In particular, the interplay between crossbridges and sarcomere length has significant impacts on the functional structural change of the C-domain of cTnI in the relaxed state. These novel observations suggest the importance of the C-domain of cTnI and the dynamic and complex interplay between various components of myofilament in the LDA mechanism.


Brain space for a learned task: strong intraspecific evidence for neural correlates of singing behavior in songbirds.
There is a controversial issue in neuroscience whether the expansion of neural network space permits the development of more complex behavior. One of the best-known model systems for studying the relationship between brain space and behavior is song production and the associated song control system in songbirds. Although the neuroanatomical background of song production is well established, the direct link between song nuclei volumes and song traits remains puzzling. Analyses within species have provided conflicting results regarding the association between song nuclei volumes and measures of song complexity and song length. Based on a meta-analysis, we present here the results of the first synthetic review, in which we test for overall intraspecific patterns in relation to bird song and the size of associated neural tissues. We found significant positive relationships between the volume of two important song nuclei (HVC and RA) and repertoire size and song length. We assessed the importance of absolute and relative volumes, and found that a control for the covariation with the telencephalon may be important. By estimating the adequate sample size that would be needed to reach sufficient statistical power in particular studies, we conclude that previous studies finding non-significant associations between song and volumes of brain nuclei were of weak power. When we factored out the covariation between song length and repertoire size, we found that these traits may explain independently significant amount of variations in the relative volume of HVC, but not of RA. The link between the volumes of song nuclei and song features has important theoretical implications with regard to the neurobiology and evolution of bird song.


Expression of T-cell antigen receptor genes during fetal development in the thymus.
The T-cell antigen receptor is a heterodimeric molecule composed of alpha- and beta-subunits of relative molecular mass 40,000-50,000 (refs 1-6). Recently, the genes encoding both the beta- and alpha- chains have been cloned. By comparing amino-acid and nucleic-acid sequences, it is clear that these genes encode the alpha- and beta-proteins of the T-cell receptor. In addition, a third receptor-like gene, the gamma-chain gene, has been identified, which has many structural and sequence characteristics in common with the alpha- and beta-chain genes. The role of the gamma-chain gene in T-cell development is unknown. We have reported recently that the beta-chain genes are transcriptionally turned on in the thymus at about day 17 of fetal development. Here we report that the alpha-chain also is transcriptionally activated during this time, but that the gamma-chain gene is active in the thymus at day 14, reaches a peak steady-state level at day 15 and rapidly declines thereafter. If the gamma-chain gene has a functional role, it would seem to be involved very early in T-cell development, before the mature T-cell receptor is expressed.


An ultrastructural study of homoclonal and heteroclonal encounters between stolons in Podocoryne carnea M. Sars (Hydroidea, Athecata).
The various phases of homo- and heteroclonal encounters between stolons of Podocoryne carnea M. Sars have been studied with the light and electron microscope. The first clone-unspecific actions and reactions to an imminent encounter between the outgrowing tip of stolon and the subterminal part of an opposed homologous organ consists in a thickening of the ectoderm of both opponents. Presumably by enzymatic means the "attacking" stolonial tip dissolves the cuticular periderm of the "attacked" stolon, which in turn counteracts by synthesizing new periderm at the site of contact. In homoclonal encounters this counteraction is overcome by the lytic efforts of the advancing tip such as to allow it to anastomose with its opponent. In heteroclonal encounters, however, the periderm secretion enacted by the "attacked" stolon successfully counteracts the lytic activities of the "attacking" tip which eventually desists from its efforts and proceeds by moving over or alongside its reluctant opponent without having produced a fusion. In no cases is the recognition of "self" or "non-self" a consequence of direct contacts between cellular surfaces. The information, of still unknown nature, must in this instance be exchanged across the cuticular periderm which covers the stolons.


Hepatic [14C]aminopyrine demethylation capacity after portocaval shunting. Comparative study in patients with and without arterialization of portal vein.
The [14C]aminopyrine breath test (ABT) was used before and after surgical portocaval shunting in 29 cirrhotic patients, 15 with arterialization of the portal vein and 14 without. These two subgroups were comparable with regard to age, prothrombin time, serum albumin, serum total bilirubin concentrations, Child classification, and preoperative ABT. After portocaval shunt, a striking reduction in ABT values was observed after 6 and 12 months (90.7 +/- 8.0%, P < 0.05 and 77.3 +/- 7.5%, P < 0.005, respectively). No further decrease was observed between 12 and 24 months. The microsomal function was reduced to a greater extent in patients with postnecrotic cirrhosis (55 +/- 4.8%, P < 0.01) than in those with alcoholic cirrhosis (84.8 +/- 10.4%, P < 0.05). Arterialization of the portal stump of the portal vein did not prevent the reduction in hepatocellular function. No significant change in prothrombin time, serum albumin, or bilirubin concentrations was observed during the follow-up period in any of the groups. Overall, preoperative ABT was significantly higher in those surviving one year (0.29 +/- 0.12% administered dose) than in those who died within this time period (0.12 +/- 0.01%, P < 0.005). This observation suggests that portocaval anastomosis induces an early decrease in microsomal function that is not prevented by arterialization of the portal vein. It also suggests that ABT might be helpful in selecting patients for shunt surgery.


Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis.
While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreERT2-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2+ cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic KrasG12D-targeted Tff2+ cells are resistant to PDAC initiation. However, KrasG12D activation in Tff2+ cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2+ cells prior to KrasG12D activation in Mist1+ acinar or Dclk1+ FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis.


Relationship between growth hormone deficiency and nonalcoholic fatty liver disease in patients with pituitary stalk interruption syndrome.
Pituitary stalk interruption syndrome (PSIS), characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary, and an ectopic posterior pituitary, can lead to congenital combined pituitary hormone deficiency. There is a high prevalence of various metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), in this population. To investigate the characteristics of NAFLD in Chinese adult patients with PSIS and its association with growth hormone deficiency. Retrospective cross-sectional study in a tertiary referral center of China. Adult patients with PSIS diagnosed, followed up between September 2019 and August 2021, were consecutively enrolled. Abdominal ultrasonography images were evaluated and noninvasive fibrosis scores were determined to assess the severity of NAFLD. Anthropometric, clinical, and biochemical parameters were compared between patients with and without NAFLD. Logistic regression was performed to assess the independent effects of insulin-like growth factor-1 (IGF-1) on NAFLD. A total of 93 patients (77 men, 16 women, mean age: 29.6 ± 7.1 years) were included. The prevalence of NAFLD and advanced fibrosis/cirrhosis was 50.5% and 4.3%, respectively. Insufficient hormone therapy and prominent metabolic disorders, including central obesity, dyslipidemia, insulin resistance, and metabolic syndrome, were more common in the NAFLD (+) group. After adjusting for multiple variables, IGF-1 <-2 standard deviation score (SDS) was found to be associated with an increased prevalence of NAFLD (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 1.21-24.55, p = .035). Per 1 SDS increase in IGF-1 was associated with a 27% lower risk of NAFLD (OR: 0.73, 95% CI: 0.52-0.97, p = .042). NAFLD is a frequent comorbidity among Chinese adult patients with PSIS and is strongly associated with lower IGF-1 levels. Timely and appropriate hormone replacement, particularly growth hormone may contribute to decreasing the risk of NAFLD in these patients.


Partial nephrectomy in surgical treatment of calculous disease.
Of a total of 158 partial nephrectomies, a detailed follow-up for up to sixteen years was obtained in 131. The rate of true ipsilateral recurrences was 26 per cent. Computer analysis of various parameters indicated that a previous history of a stone in the same or the contralateral kidney, or the presence of multiple or scattered stones in the affected side, were associated with a particularly high recurrence rate. Urinary infection at the time of or prior to operation was not of prognostic significance. The importance of complete excision of the calyceal neck was confirmed. It was concluded that the operation is logical for removal of a diseased segment of kidney, but generally cannot be recommended in the hope of removing a stone-bearing area of kidney and hence reducing the recurrence rate.