Sheltered homeless children: their eligibility and unmet need for special education evaluations.
This study described the proportion of sheltered homeless children in Los Angeles, Calif, who were eligible for special education evaluations because of a probable behavioral disorder, learning disability, or mental retardation, and to explore their level of unmet need for special education services. This was a cross-sectional study of 118 parents and 169 children aged 6 through 12 years living in 18 emergency homeless family shelters in Los Angeles County, California. Parents and children were interviewed with standardized mental health and academic skill measures in English and Spanish. Almost half (45%) of the children met criteria for a special education evaluation, yet less than one quarter (22%) had ever received special education testing or placement. The main point of contact for children with behavioral disorders and learning problems was the general health care sector. School-aged sheltered homeless children have a high level of unmet need for special education evaluations, the first step toward accessing special education programs. Interventions for homeless children should include integration of services across special education, general health care, and housing service sectors.


Blended cumin/Zanthoxylum essential oil improve the antibacterial, fresh-keeping performance and flavor of chilled fresh mutton.
Microbial pollution and fat oxidation are the main factors that induce the deterioration in the quality of chilled fresh mutton. This study evaluated the effects of cumin (Cuminum cyminum) essential oil (CEO), Zanthoxylum essential oil (ZEO), and blended cumin/zanthoxylum essential oil (BEO) on the antibacterial, preservation of freshness, and flavor improvement of chilled fresh mutton. The results show that BEO exerts a good inhibition effect on microbial growth, lipid oxidation, and the formation of TVB-N, as well as slowing down the rate of juice loss under chilled conditions. GC-IMS assay results showed that BEO can enrich the flavor of roasted mutton with a higher level of volatile organic substances, such as ethyl acetate D. In conclusion, BEO treatments were more efficient than single treatments in ensuring the quality of lamb to improve microbiological safety and improve the flavor of roasted lamb stored under chilled conditions. Overall research indicates that BEO is an effective natural addition that can be used to preserve the quality and safety of chilled fresh mutton during storage.


Knife-edged crown fabricated by 3-dimensional gel deposition and soft milling.
Restorations with knife-edge margins are more prone to margin chipping during the manufacturing process. Three-dimensional gel deposition shows potential for fabricating zirconia restorations with good margin quality, but studies on its performance in fabricating knife-edged crowns are lacking. The purpose of this in vitro study was to compare the 3-dimensional trueness, surface morphology, and margin quality of self-glazed zirconia and soft-milled zirconia crowns with knife-edge margins. An abutment with a knife-edge finish line design was prepared and scanned with a laboratory scanner. Anatomic contour crowns were designed and fabricated by 3-dimensional gel deposition and soft milling (n=5). The crowns were digitalized, and the scan data were superimposed on the computer-aided design (CAD) data for 3-dimensional deviation analysis. Surface morphology and margin quality were characterized with microscopic examination. The self-glazed zirconia crowns showed a smooth and glossy appearance. The soft-milled crowns showed traces left by the removal of support bars and numerous micropits of various sizes. In internal areas, no significant difference was found in root mean square values between the 2 groups (P>.05). For the external surface, self-glazed zirconia showed statistically lower root mean square values than the soft-milled crowns (P<.05). When observed at ×5 magnification, all the self-glazed zirconia crowns showed smooth edges with no defects, whereas small or large margin defects were found in the soft-milled crowns. When characterized at ×200 magnification, minor margin flaws were observed in the self-glazed zirconia crowns. More and larger margin defects were found in the soft-milled crowns. Three-dimensional gel deposition forms a smoother and more homogeneous surface than soft milling. Knife-edged self-glazed zirconia crowns have good dimensional accuracy and margin quality.


Increased chin muscle tone during all sleep stages in children taking selective serotonin reuptake inhibitor antidepressants and in children with narcolepsy type 1.
To assess if selective serotonin reuptake inhibitor (SSRI) antidepressants are able to modify the chin electromyogram (EMG) tone during sleep also in children. Twenty-three children and adolescents (12 girls, mean age 14.1 years, SD 2.94) under therapy with antidepressant for their mood disorder were consecutively recruited and had a PSG recording. Twenty-one were taking were taking SSRI and treatment duration was 2-12 months. An age- and sex matched group of 33 control children (17 girls, mean age 14.2 years, SD 2.83) and 24 children with narcolepsy type 1 (12 girls, mean age 13.7 years, SD 2.80) were also included. The Atonia Index was then computed for each NREM sleep stage and for REM sleep, also all EMG activations were counted. Atonia Index in all sleep stages was found to be significantly reduced in children with narcolepsy followed by the group taking SSRI antidepressants and the number of EMG activations was also increased in both groups. Fluoxetine, in particular, was found to be significantly associated with reduced Atonia index during NREM sleep stages N1, N2, and N3, and with an increased number of EMG activations/hour during sleep stage N3. Similarly to adults, SSRI antidepressants are able to modify the chin EMG tone in children during REM sleep, as well as during NREM sleep stages. Different pharmacological properties of the different SSRI might explain the differential effect on chin tone during sleep found in this study.


Time course of ovarian tumour growth in soft agar culture.
Single time point assessment is usually employed in the Human Tumour Cloning System as the only parameter for in vitro growth. This does not seem to give a fair expression of the dynamic biological properties of tumour growth and time dependent effects, e.g. of cytotoxic drugs. We studied the time course of colony formation in temporal growth patterns (TGPs) and compared this method of growth evaluation with conventional single time point assessment in 57 samples of ovarian tumour cultures in the HTCS. A first advantage of the use of TGPs is that more cultures become evaluable, as this assessment over time can detect a rise in the number of colonies in dishes where colony-like clumps have initially been seeded. Thus only 28 of the cultures were evaluable for single time point assessment, whereas 57 were available for TGP evaluation. Growth was more often seen at TGP evaluation (14/57) than at single day assessment (8/57). Evaluation of growth over the course of time potentially allows detection of sensitivity to drugs. Furthermore TGPs reflect the dynamics of biological growth. These features cannot be studied in single time point assessment.


Double Mutations in Succinate Dehydrogenase Are Involved in SDHI Resistance in Corynespora cassiicola.
With the further application of succinate dehydrogenase inhibitors (SDHI), the resistance caused by double mutations in target gene is gradually becoming a serious problem, leading to a decrease of control efficacy. It is important to assess the sensitivity and fitness of double mutations to SDHI in Corynespora cassiicola and analysis the evolution of double mutations. We confirmed, by site-directed mutagenesis, that all double mutations (B-I280V+D-D95E/D-G109V/D-H105R, B-H278R+D-D95E/D-G109V, B-H278Y+D-D95E/D-G109V) conferred resistance to all SDHI and exhibited the increased resistance to at least one fungicide than single point mutation. Analyses of fitness showed that all double mutations had lower fitness than the wild type; most of double mutations suffered more fitness penalties than the corresponding single mutants. We also further found that double mutations (B-I280V+D-D95E/D-G109V/D-H105R) containing low SDHI-resistant single point mutation (B-I280V) exhibited higher resistance to SDHI and low fitness penalty than double mutations (B-H278Y+D-D95E/D-G109V) containing high SDHI-resistant single mutations (B-H278Y). Therefore, we may infer that a single mutation conferring low resistance is more likely to evolve into a double mutation conferring higher resistance under the selective pressure of SDHI. Taken together, our results provide some important reference for resistance management.


Association Between the Patient Driven Payment Model and Therapy Utilization and Patient Outcomes in US Skilled Nursing Facilities.
In October 2019, Medicare changed its skilled nursing facility (SNF) reimbursement model to the Patient Driven Payment Model (PDPM), which has modified financial incentives for SNFs that may relate to therapy use and health outcomes. To assess whether implementation of the PDPM was associated with changes in therapy utilization or health outcomes. This cross-sectional study used a regression discontinuity (RD) approach among Medicare fee-for-service postacute-care patients admitted to a Medicare-certified SNF following hip fracture between January 2018 and March 2020. Skilled nursing facility admission after PDPM implementation. Main outcomes were individual and nonindividual (concurrent and group) therapy minutes per day, hospitalization within 40 days of SNF admission, SNF length of stay longer than 40 days, and discharge activities of daily living score. The study cohort included 201 084 postacute-care patients (mean [SD] age, 83.8 [8.3] years; 143 830 women [71.5%]; 185 854 White patients [92.4%]); 147 711 were admitted pre-PDPM, and 53 373 were admitted post-PDPM. A decrease in individual therapy (RD estimate: -15.9 minutes per day; 95% CI, -16.9 to -14.6) and an increase in nonindividual therapy (RD estimate: 3.6 minutes per day; 95% CI, 3.4 to 3.8) were observed. Total therapy use in the first week following admission was about 12 minutes per day (95% CI, -13.3 to -11.3) (approximately 13%) lower for residents admitted post-PDPM vs pre-PDPM. No consistent and statistically significant discontinuity in hospital readmission (0.31 percentage point increase; 95% CI, -1.46 to 2.09), SNF length of stay (2.7 percentage point decrease in likelihood of staying longer than 40 days; 95% CI, -4.83 to -0.54), or functional score at discharge (0.04 point increase in activities of daily living score; 95% CI, -0.19 to 0.26) was observed. Nonindividual therapy minutes were reduced to nearly zero in late March 2020, likely owing to COVID-19-related restrictions on communal activities in SNFs. In this cross-sectional study of SNF admission after PDPM implementation, a reduction of total therapy minutes was observed following the implementation of PDPM, even though PDPM was designed to be budget neutral. No significant changes in postacute outcomes were observed. Further study is needed to understand whether the PDPM is associated with successful discharge outcomes.


[Enhancement of compensatory renal hypertrophy by beta-1-24 corticotropin in the rat].
In the rat, the administration of beta1-24-corticotrophin during 7 days following an uninephrectomy enhances significantly the compensatory hypertrophy of the remaining kidney. There is no increase in renal compensatory hypertrophy when ACTH is injected to previously adrenalectomized rats. This action of ACTH could be related to the diabetes mellitus induced by this hormone or to an increase in sodium reabsorption by the tubular epithelial cells.


Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer.
Maintenance of the intestinal epithelium is dependent on the control of stem cell (SC) proliferation and differentiation. The fine regulation of these cellular processes requires a complex dynamic interplay between several signaling pathways, including Wnt, Notch, Hippo, EGF, Ephrin, and BMP/TGF-β. During the initiation and progression of colorectal cancer (CRC), key events, such as oncogenic mutations, influence these signaling pathways, and tilt the homeostatic balance towards proliferation and dedifferentiation. Therapeutic strategies to specifically target these deregulated signaling pathways are of particular interest. However, systemic blocking or activation of these pathways poses major risks for normal stem cell function and tissue homeostasis. Interestingly, long non-coding RNAs (lncRNAs) have recently emerged as potent regulators of key cellular processes often deregulated in cancer. Because of their exceptional tissue and tumor specificity, these regulatory RNAs represent attractive targets for cancer therapy. Here, we discuss how lncRNAs participate in the maintenance of intestinal homeostasis and how they can contribute to the deregulation of each signaling pathway in CRC. Finally, we describe currently available molecular tools to develop lncRNA-targeted cancer therapies.


Effects of surgical face masks on cardiopulmonary parameters during steady state exercise.
Wearing face masks reduce the maximum physical performance. Sports and occupational activities are often associated with submaximal constant intensities. This prospective crossover study examined the effects of medical face masks during constant-load exercise. Fourteen healthy men (age 25.7 ± 3.5 years; height 183.8 ± 8.4 cm; weight 83.6 ± 8.4 kg) performed a lactate minimum test and a body plethysmography with and without masks. They were randomly assigned to two constant load tests at maximal lactate steady state with and without masks. The cardiopulmonary and metabolic responses were monitored using impedance cardiography and ergo-spirometry. The airway resistance was two-fold higher with the surgical mask (SM) than without the mask (SM 0.58 ± 0.16 kPa l-1 vs. control [Co] 0.32 ± 0.08 kPa l-1; p < 0.01). The constant load tests with masks compared with those without masks resulted in a significantly different ventilation (77.1 ± 9.3 l min-1 vs. 82.4 ± 10.7 l min-1; p < 0.01), oxygen uptake (33.1 ± 5 ml min-1 kg-1 vs. 34.5 ± 6 ml min-1 kg-1; p = 0.04), and heart rate (160.1 ± 11.2 bpm vs. 154.5 ± 11.4 bpm; p < 0.01). The mean cardiac output tended to be higher with a mask (28.6 ± 3.9 l min-1 vs. 25.9 ± 4.0 l min-1; p = 0.06). Similar blood pressure (177.2 ± 17.6 mmHg vs. 172.3 ± 15.8 mmHg; p = 0.33), delta lactate (4.7 ± 1.5 mmol l-1 vs. 4.3 ± 1.5 mmol l-1; p = 0.15), and rating of perceived exertion (6.9 ± 1.1 vs. 6.6 ± 1.1; p = 0.16) were observed with and without masks. Surgical face masks increase airway resistance and heart rate during steady state exercise in healthy volunteers. The perceived exertion and endurance performance were unchanged. These results may improve the assessment of wearing face masks during work and physical training.


Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study.
Outcome studies in patients with anoxic-ischemic encephalopathy focus on the early and reliable prediction of an outcome no better than a vegetative state or severe disability. We determined the effect of mild therapeutic hypothermia on the validity of the currently used clinical practice parameters. We conducted a retrospective cohort study of adult comatose patients after cardiac arrest treated with hypothermia. All data were collected from medical charts and laboratory files and analyzed from the day of admission to the intensive care unit until day 7, discharge from the intensive care unit or death using the Utstein definitions for the registration of the data. We analyzed the data of 103 patients. The combination of an M1 or M2 on the Glasgow Coma Scale or absent pupillary reactions or absent corneal reflexes on day 3 was present in 80.6% of patients with an unfavourable and 11.1% of patients with a favourable outcome. The combination of M1 or M2 and absent pupillary reactions to light and absent corneal reflexes on day 3 was present in 14.9% of patients with an unfavourable and none of the patients with a favourable outcome. None of the patients with a favourable outcome had a bilaterally absent somatosensory evoked potential of the median nerve. The value of electroencephalogram patterns in predicting outcome was low, except for reactivity to noxious stimuli. No single clinical or electrophysiological parameter has sufficient accuracy to determine prognosis and decision making in patients after cardiac arrest, treated with hypothermia.


[Surgical treatment of pulmonary carcinoids - ten-year results].
Carcinoids are malignant neuro-endocrine tumours occurring in the bronchopulmonary location in about 25 %, and accounting for approximately 2 % of all pulmonary tumours. Our retrospective analysis included 27 patients, 14 men and 13 women, mean age 58.4 years, treated from 2000 to 2009 for carcinoids in bronchopulmonary locations. The tumour manifested clinically in 52 % of the cases, the most common symptom being cough; one tumour manifested as carcinoid syndrome. All patients underwent fibrobronchoscopy that was positive in 20 cases (74.1 %). Pre-surgery histological diagnoses were made in 13 patients (48.1 %). Chest CT scans were carried out in 26 patients, and the investigation failed to detect the expected pathological process in 2 of the patients. Octreoscans were carried out in 12 patients, and were successful in identifying a primary neuroendocrine tumour in 75 %. All patients in the sample underwent rad-ical surgical therapy; the most common surgical procedure was lobectomy (70.4 %). Perioperative morbidity and mortality were zero. Typical carcinoids were found in 20 cases while 7 cases were atypical carcinoids, 20 tumours were located centrally. 74 % of the tumours were consistent with stage I A disease. Mean follow-up period was 47 (range: 6-134) months. Local recurrences were observed in 2 patients (7.4 %), but the tumour disseminated in 4 patients (14.8 %). Two patients (7.4 %) died during the follow-up period. Overall five-year survival in the sample was 92.3 %, 90.9 % in the typical carcinoid group and 100 % for atypical carcinoids. We found a statistically significant association between disease-free interval and histological type of the tumour; the risk of progression was 8 times higher in -patients with atypical carcinoids compared to patients with typical carcinoids (Log-Rank-Test: p-value = 0.0049). Radical surgical treatment of bronchopulmonary carcinoids is the optimum therapeutic approach that results in the best results both regarding perioperative morbidity and mortality and regarding long-term survival of the patients.


Early experience with the intraluminal graft prosthesis.
Surgical therapy for dissection of the thoracic aorta has been associated with a high mortality rate due in part to intraoperative bleeding at the suture lines and through the prosthesis. A technique has been devised to obviate some of these problems which utilizes a sutureless prosthesis that can be placed within the aorta. This device is now commercially available. Because of the infrequent use and the need to maintain a wide variety of lengths and diameters of these grafts, several Portland area hospitals jointly purchased grafts to reduce inventory and cost. From November 1981 through September 1982, four patients in two Portland area hospitals were treated with intraluminal grafts for descending thoracic dissections. All patients survived the surgical treatment and were discharged without complications. Based on a review of the literature and our initial experience, the intraluminal prosthesis appears to represent a significant improvement over conventional graft placement for treatment of both acute and chronic aortic dissection.


Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.
Immature B cells developing in the bone marrow are found in the parenchyma and sinusoids. The mechanisms that control the positioning of B cells in the sinusoids are not understood. Here we show that the integrin alpha(4)beta(1) (VLA-4) and its ligand VCAM-1 were required, whereas the chemokine receptor CXCR4 was dispensable, for sinusoidal retention of B cells. Instead, cannabinoid receptor 2 (CB2), a Galpha(i) protein-coupled receptor upregulated in immature B cells, was required for sinusoidal retention. Using two-photon microscopy, we found immature B cells entering and crawling in sinusoids; these immature B cells were displaced by CB2 antagonism. Moreover, CB2-deficient mice had a lower frequency of immunoglobulin lambda-chain-positive B cells in the peripheral blood and spleen. Our findings identify unique requirements for the retention of B cells in the bone marrow sinusoidal niche and suggest involvement of CB2 in the generation of the B cell repertoire.


Angioscopy of arm vein infrainguinal bypass grafts.
Between January 1988 and December 1990, 56 patients underwent 66 arm vein infrainguinal bypass grafts for limb salvage. Thirty-nine grafts were intraoperatively monitored by the standard methods of continuous wave Doppler alone (30) and arteriography (9). Twenty-seven grafts were prepared and monitored by intraoperative angioscopy. No significant findings requiring intraoperative revision or correction were noted in the grafts monitored by the standard methods. However, in those grafts prepared and monitored by angioscopy, intraluminal abnormalities of the arm veins were detected and corrected in 20/27 (74%). None of the grafts prepared or monitored by angioscopy occluded within 30 days, whereas, in those grafts monitored by continuous wave Doppler and arteriography, 7/39 failed within 30 days, a primary patency rate of 32/39 (82%) (x2 with yates correction, p = 0.055). This study shows that angioscopic preparation and monitoring of arm vein bypass grafts allows the detection and correction of unsuspected intraluminal abnormalities, which appears to improve the early primary patency of arm vein infrainguinal bypass grafts.


Experimental study of sono-crystallisation of ZnSO4·7H2O, and interpretation by the segregation theory.
Power ultrasound is known to enhance crystals nucleation, and nucleation times can be reduced by one up to three orders of magnitude for several organic or inorganic crystals. The precise physics involved in this phenomenon still remains unclear, and various mechanisms involving the action of inertial cavitation bubbles have been proposed. In this paper, two of these mechanisms, pressure and segregation effects, are examined. The first one concerns the variations of supersaturation induced by the high pressures appearing in the neighbourhood of a collapsing bubble, and the second one results from the modification of clusters distribution in the vicinity of bubble. Crystallisation experiments were performed on zinc sulphate heptahydrate ZnSO(4)·7H(2)O, which has been chosen for its pressure-independent solubility, so that pressure variations have no effect on supersaturation. As observed in past studies on other species, induction times were found lower under insonification than under silent conditions at low supersaturations, which casts some doubts on a pure pressure effect. The interfacial energy between the solid and the solution was estimated from induction times obtained in silent conditions, and, using classical nucleation theory, the steady-state distribution of the clusters was calculated. Segregation theory was then applied to calculate the over-concentrations of n-sized clusters at the end of the collapse of a 4 μm bubble driven at 20 kHz by different acoustic pressures. The over-concentration of clusters close to the critical size near a collapsing bubble was found to reach more than one order of magnitude, which may favour the direct attachment process between such clusters, and enhance the global nucleation kinetics.


Unilateral Möbius syndrome: two cases and a review of the literature.
The Möbius sequence is a rare condition defined by the combination of congenital non-progressive facial and abducens nerve palsies. The etiology of the sequence is still unknown, but likely encompasses a group of heterogeneous disorders involving genetic maldevelopment of the brainstem, a fetal vascular insult and/or teratogen exposure. The clinical phenotype reported has expanded over the years, and may be associated with more extensive cranial nerve and oropharyngeal involvement, as well as limb defects. We describe two cases of children presenting with unilateral Möbius syndrome associated with ipsilateral unilateral palatal weakness. Investigations failed to identified a clear underlying etiology, but both cases shared phenotypic features of other more common cranial facial disorders such as craniofacial microsomia and the velocardiofacial syndrome. These two cases highlight the clinical heterogeneity of the Möbius sequence. Although asymmetries are not uncommon, cases with strictly unilateral features are extremely rare, and as such these may represent a distinct subgroup that may pertain to a specific etiology. Although in many cases, evidence of an intrauterine vascular insult may be identified, a contributing genetic etiology should be considered, even in cases with strictly unilateral features. As such genes expressed in the developing rhombencephalon and its vasculature represent good candidates for future investigation.


Molecular characterization of calicivirus strains detected in outbreaks of gastroenteritis in Argentina.
Eight outbreaks of acute gastroenteritis occurred in Argentina in 2004 were tested for the presence of Calicivirus, Rotavirus and Astrovirus as possible causative agents. Caliciviruses were found in 39 out of the 100 tested samples, followed by six Astrovirus-positive samples and two Rotavirus-positive samples. Thirty-seven out of the 39 Calicivirus-positive samples were typed as Norovirus while the remaining two were typed as Sapovirus. Sequence and phylogenetic analyses of 13 Norovirus-positive samples revealed the presence of strains from the genogroups GI, GII, and GIV. Six Norovirus strains were grouped with the GIV-1 strains, three with the GIIb strains, two with the Farmington Hill-cluster (GII-4) strains, and the remaining two with the GI strains. To our knowledge, this study constitutes the first report of molecular epidemiology of human Caliciviruses associated to gastroenteritis outbreaks in Argentina and the circulation of GIIb and GIV-1 strains in South-America.


Investigation of natural and anthropogenic hydrocarbon inputs in sediments using geochemical markers. I. Santos, SP--Brazil.
A study on the inputs of organic matter to marine sediments of Santos Bay and Estuary, located in southeastern São Paulo State, Brazil, is presented here. The following geochemical markers were identified and quantified: aliphatic hydrocarbons (normal and isoprenoid alkanes), petroleum biomarkers, linear alkylbenzenes (LABs) and polycyclic aromatic hydrocarbons (PAHs). Sediment samples, collected at 15 sites in the bay and surrounding channels, were extracted and analyzed by gas chromatography with flame ionization and mass spectrometer detectors. Total concentrations varied from 0.17 to 107.80 microg g(-1) for aliphatics, from 47.2 to 2560.1 ng g(-1) for petroleum biomarkers, from 16.9 to 430.6 ng g(-1) for LABs and from 79.6 to 15389.1 ng g(-1) for PAHs. Anthropogenic contributions were apparent, indicating the influences of the Cubatao industrial complex, sewage outfalls along the area, the waste deposit of Santos city and storage facilities for petroleum and derivatives, based on the higher concentrations of geochemical markers detected.


Costs associated with blood transfusions in Sweden--the societal cost of autologous, allogeneic and perioperative RBC transfusion.
Anaemia is characterised by an insufficient number of red blood cells (RBCs) and might occur for different reasons, e.g. surgical procedures are often with associated blood loss. Patients who suffer from anaemia have the option of treatment with blood transfusion or medical treatment. In this study, the societal cost, for the case of Sweden, of RBC transfusion using three different techniques, i.e. allogeneic, autologous and intraoperative transfusion, was estimated. The analysis was based on information from interviews with hospital staff at large Swedish hospitals and from published data. The average cost for a 2 units transfusion was found to be Swedish kronor (SEK) 6330 (702 Euro) for filtered allogeneic RBCs and SEK 5394 (598 Euro) for autologous RBCs for surgery patients. Transfusion reactions accounted for almost 35 per cent of the costs of allogeneic RBC transfusions. The administration cost was found to be much higher for autologous transfusions compared with allogeneic transfusions. The cost of intraoperative erythrocyte salvage was calculated to be SEK 2567 (285 Euro) per transfusion (>4 units).


Sperm cryopreservation and in vitro fertilization.
Since the mouse has become the most profound model system to investigate the genetics and pathogenetics of human diseases, a huge number of new mutant mouse strains has been generated and still a lot effort is being done to increase the number of suitable mouse models. In nearly all animal facilities the maintenance of breeding colonies is limited and the mouse strains have to be archived in a reliable way. Mouse sperm cryopreservation provides an efficient management of these genetic resources by reducing maintenance space and cost and by safeguarding them against, for example, disease, breeding failure, and genetic drift.The sperm archiving method has been proven extensively in large-scale ENU mutagenesis programs and in mouse repository and resource centers worldwide (Federation of International Mouse Resources, http://www.fimre.org ). Nevertheless, it is crucial to select accurately the most suitable archiving procedure, or combination of different archiving procedures, for each individual mouse mutant strain.


Cholecystostomy.
The role of cholecystostomy in the sugical treatment of gallstones has been considered. In a consecutive series of 558 patients who underwent surgery for gallstones, 30 (5-4 per cent) had cholecystostomy alone and a further 17 (3-1 per cent) cholecystostomy combined with exploration of the bile ducts. Cholecystostomy was done because cholecystectomy was technically very hazardous in 15 patients. In the remaining patients cholecystostomy was preferred to cholecystectomy because o f the poor general condition of the patient or the presence of pancreatitis. Of the 47 patients submitted to cholecystostomy, 2(4-2 per cent) died postoeratively and 4(8-4 percent) subsequently underwent cholecystectomy. Of 24 patients who were available for long term follow-up, only 1 patient had pain which was definitely considered to be due to gallstones, although 3 other patients also had abdominal pain, while 7 patients showed radiological evidience of gallstones. It is contended that cholecystostomy has a small but definite part to play in the immediate surgical treatment of gallstones and that the long term results of the operation are sufficiently good to justify its use in selected patients.


Unconscious vision and executive control: how unconscious processing and conscious action control interact.
Research on unconscious or unaware vision has demonstrated that unconscious processing can be flexibly adapted to the current goals of human agents. The present review focuses on one area of research, masked visual priming. This method uses visual stimuli presented in a temporal sequence to lower the visibility of one of these stimuli. In this way, a stimulus can be masked and even rendered invisible. Despite its invisibility, a masked stimulus if used as a prime can influence a variety of executive functions, such as response activation, semantic processing, or attention shifting. There are also limitations on the processing of masked primes. While masked priming research demonstrates the top-down dependent usage of unconscious vision during task-set execution it also highlights that the set-up of a new task-set depends on conscious vision as its input. This basic distinction captures a major qualitative difference between conscious and unconscious vision.


[Direct stent implantation in acute myocardial infarction. The DISCO 3 study].
An association has been reported between direct stenting in primary angioplasty and low incidences of the no-reflow phenomenon and distal embolization. The aims of this study were to determine the proportion of patients who can be treated by direct stent implantation and to identify factors that establish when the technique should be used in acute myocardial infarction in clinical practice. This prospective descriptive and multicenter study (DISCO 3) included 189 patients. Angiographic reperfusion parameters were recorded and resolution of the ST-segment elevation was monitored. Adverse clinical events, such as death, non-fatal reinfarction and repeat revascularization of the culprit vessel, were recorded at discharge, and after one and six months. Direct stenting was performed in 56% of patients, and stenting after predilatation in 44%. The main predictors of direct stenting were short postinfarction delay, non-zero initial TIMI flow, and preinfarction angina. The most common reasons for balloon predilatation were TIMI flow zero on traversing the lesion with a guidewire (92%), involvement of a major bifurcation or tortuous vessel, and severe calcification. Indices of myocardial reperfusion were better with direct stenting: TIMI myocardial perfusion grade 2-3 flow was present in 84% vs 69% (P=.005), and > 70% ST-segment resolution occurred in 66% vs 42% (P=.003). No difference in adverse clinical events was found. Direct stenting is feasible for treating acute myocardial infarction in more than half of patients. The lesions should not be severely calcified nor involve tortuous vessels, and there should be sufficient flow following passage of a guidewire to define the lesion's characteristics.


Resolving the Instructions for αβ T Cell Development.
In this issue of Immunity, Chopp et. al. use single-cell transcriptomics and epigenomics in mice and human samples to delineate developmental trajectories of αβ T cell subsets and refine the kinetic selection model of CD4+ and CD8+ T cell lineage commitment.


Movement Disorders in Children.
Movement disorders represent a common presentation in pediatrics and are often a source of clinical and diagnostic dilemmas. In this review, we provide an overview of common causes along with simplified clinical approach and management options for major movement disorders. This narrative review is based on contemporary evidence and personal experience. Medline was searched for recent advances, current understanding and consensus on classification, clinical features, diagnosis and treatment. Movement disorders are classified as hyperkinetic and hypokinetic disorders, the latter being rare in childhood. The hyperkinetic disorders include dystonia, chorea, athetosis, tics and tremor, stereotypies, myoclonus, startle syndromes and functional disorders. Some movement disorders can be benign and developmental. A large proportion of conditions are genetic in origin with a guarded prognosis. Some of the conditions may be post-infectious, immune-mediated or drug induced. Multiple types of movement disorders are present in many conditions. The age at onset, type and distribution of abnormal movements and presence of associated neurological and systemic features help in narrowing the differential diagnosis. The pharmacotherapy of movement disorders is complex and evolving. A synopsis of movement disorders presenting in pediatric age has been provided, incorporating the latest evidence. A simplified approach for clinical diagnosis has been developed for dystonia and chorea.


Did field marshal bernard montgomery (montgomery of alamein) have asperger's syndrome?
In the present paper the evidence for Field Marshal Montgomery having Asperger's syndrome is examined. Biographies of Montgomery were examined to search for evidence that he met criteria for Asperger's syndrome - Gillberg (1991) and Asperger's disorder (APA.1994) and Anankastic personality disorder (WHO,1992). He demonstrates a qualitative impairment in social interaction and restricted repetitive and stereotyped patterns of behaviour, interests and activities. It can be concluded that he met criteria for Asperger's disorder DSM-IV (APA.1994).


Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT.
This retrospective analysis compared two regimens of fludarabine combined with i.v. BU 6.4 mg/kg (FB2) or BU 12.8 mg/kg (FB4) for allografting of AML in first CR. A total of 437 patients (median age: 50 years) were administered FB2 (n = 225, 51%) or FB4 (n = 212, 49%). Median follow-up time was 28 months. Use of FB2 resulted in a longer time to neutrophil engraftment (17 vs 15 days, P < 0.0001) but no difference in incidence of grade II-IV acute (P = 0.54) or chronic GVHD (P = 0.51). In patients < 50 years of age, FB2 was associated with a higher 2-year cumulative incidence of relapse (33 ± 6% vs 20 ± 4%, P = 0.04), but there was no difference in 2-year leukemia-free survival (LFS) (P = 0.45), OS (P = 0.53) or non-relapse mortality (P = 0.17). In recipients ⩾ 50 years of age, FB2 resulted in better 2-year LFS (63 ± 4% vs 42 ± 7%, P = 0.02) and OS (68 ± 4% vs 45 ± 7%, P = 0.006); a lower 2-year non-relapse mortality, albeit not statistically significant (15 ± 3% vs 29 ± 6%, P = 0.06), was observed with FB2. FB2 is an effective and well-tolerated regimen in patients ⩾ 50 years of age and does not compromise survival when used in patients <50 years undergoing allogeneic transplantation for AML in first CR.


Identification of knowledge translation theories, models or frameworks suitable for health technology reassessment: a survey of international experts.
Health technology reassessment (HTR) is a field focused on managing a technology throughout its life cycle for optimal use. The process results in one of four possible recommendations: increase use, decrease use, no change or complete withdrawal of the technology. However, implementation of these recommendations has been challenging. This paper explores knowledge translation (KT) theories, models and frameworks (TMFs) and their suitability for implementation of HTR recommendations. Cross-sectional survey. Purposeful sampling of international KT and HTR experts was administered between January and March 2019. Sixteen full-spectrum KT TMFs were rated by the experts as 'yes', 'partially yes' or 'no' on six criteria: familiarity, logical consistency/plausibility, degree of specificity, accessibility, ease of use and HTR suitability. Consensus was determined as a rating of ≥70% responding 'yes'. Descriptive statistics and manifest content analysis were conducted on open-ended comments. Eleven HTR and 11 KT experts from Canada, USA, UK, Australia, Germany, Spain, Italy and Sweden participated. Of the 16 KT TMFs, none received ≥70% rating. When ratings of 'yes' and 'partially yes' were combined, the Consolidated Framework for Implementation Research was considered the most suitable KT TMF by both KT and HTR experts (86%). One additional KT TMF was selected by KT experts: Knowledge to Action framework. HTR experts selected two additional KT TMFs: Co-KT framework and Plan-Do-Study-Act cycle. Experts identified three key characteristics of a KT TMF that may be important to consider: practicality, guidance on implementation and KT TMF adaptability. Despite not reaching an overall ≥70% rating on any of the KT TMFs, experts identified four KT TMFs suitable for HTR. Users may apply these KT TMFs in the implementation of HTR recommendations. In addition, KT TMF characteristics relevant to the field of HTR need to be explored further.


Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette-Guérin.
Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette-Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early childhood. Therefore, we first devised a system to assess the efficacy of a candidate booster vaccine. Specifically, variant strain BCG-II, a minor component of BCG-Tokyo strain, which elicits weak immunity, was administered to guinea pigs. Vaccine-induced immunity and protection against Mycobacterium tuberculosis (Mtb) infection were evaluated using skin delayed-type hypersensitivity (DTH) and Mtb colony forming unit counts in organs, respectively. Candidate booster vaccine containing the mycobacterial DNA-binding protein 1 (MDP1) as antigen and CpG oligodeoxynucleotide G9.1 as adjuvant increased T-bet expression and IFN-γ production in human peripheral blood mononuclear cells. Intradermal administration of MDP1 or MDP1 and G9.1 to unimmunized guinea pigs produced DTH on MDP1-inoculated skin. Boosting BCG-II-primed guinea pigs with this protocol effectively enhanced DTH against MDP1 and protection against Mtb infection, particularly when combined with G9.1. The candidate vaccine may contribute to efforts to prevent tuberculosis.


Effect of sex hormones on human voice physiology: from childhood to senescence.
The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account.


Angiographic perfusion score assessed in patients with acute myocardial infarction is correlated with cardiac magnetic resonance infarct size and N-terminal pro-brain natriuretic peptide in 6-month follow-up.
Angiographic Perfusion Score (APS) proposed as a simple, angiographic score linking epicardial and myocardial perfusion parameters before and after percutaneous coronary intervention (PCI) is a predictor of short-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI. Aim of the study was to analyze the correlation between APS and both infarct size and left ventricular function in long-term follow-up. In a cohort of 68 patients with STEMI treated with PCI APS was calculated for infarct-related artery based on angiographic parameters and was defined as the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (0-3 points) and the TIMI myocardial perfusion grade (0-3 points) before and after PCI (range of points from 0 to 12). Full perfusion was defined as APS ≥ 10. Cardiac magnetic resonance (CMR) parameters and N-terminal pro-brain natriuretic peptide (NT pro-BNP) were assessed at 6 months. Median APS was 7.5 points. APS ≥ 10 was present in 42% of patients. The significant correlation was found between APS and: CMR infarct size (r = - 0.48; P = 0.0001), CMR left ventricular (LV) ejection fraction (r = 0.5; P = 0.002), LV end-diastolic volume index (r = - 0.37; P = 0.004), LV end-systolic volume index (r = -0.41; P = 0.001), NT pro-BNP (r = - 0.5; P = 0.02). Patients with APS ≥ 10 had significantly lower infarct size, LV volumes, higher EF and lower NT pro-BNP. APS assessed in patients with STEMI treated with PCI is a good predictor of infarct size and left ventricular function in 6-month follow-up.


Parental psychological well-being and cognitive development of very low birth weight infants at 2 years.
To assess the associations between cognitive development of very low birth weight (VLBW) infants and measures of parental psychological well-being. In this prospective cohort study, 182 VLBW infants born 1/2001-12/2006 at the Turku University Hospital, Finland, were followed up. At 2 years corrected age, cognitive development of the child was assessed using the Mental Development Index of Bayley Scales, and both parents filled in validated questionnaires defining parental psychological well-being (Beck Depression Inventory, Parenting Stress Index and Sense of Coherence Scale). The cognitive delay of the infant was associated with paternal symptoms of depression (p = 0.007) and parenting stress (p = 0.03). Mothers of the infants with cognitive delay reported increased parenting stress related to the difficulty to accept the child (p = 0.001). Weak sense of coherence predicted depressive symptoms in both parents (p < 0.0001). Even if the fathers of VLBW infants experienced depressive symptoms less often than the mothers, the ability of the fathers to cope was significantly associated with the cognitive development of the infant. In addition, the fathers reported more parenting stress if the infant had a cognitive delay. The mothers reported more parenting stress related to accepting the VLBW infant with cognitive delay.


Early decrease in lean mass and bone mass in postmenopausal women: a cross-sectional study.
The effect of menopause transition in body composition was evaluated in a cross-sectional study. The study was carried out in an outpatient clinic of Brazil enrolling premenopausal (n = 64) and postmenopausal (n = 42) women aged between 44 and 52 years, with weight stability (±2 kg) for at least 6 months before evaluation. Participants answered a sociodemographic semi-structured questionnaire, the Menopause Rating Scale, the International Physical Activity Questionnaire, 24-h dietary recall and a visual analogue scale of appetite. Blood biochemical, anthropometry and densitometry measurements were used for body composition estimation. Most participants were overweight (31.4%) or obese (45.7%) and categorized as 'high active' in physical activity (65.7%). Lean mass and bone mass decreased in the first few years of menopause. A metabolic turn to an increase of lipids was observed, represented by greater total cholesterol and high-density lipoprotein cholesterol levels. Menopause transition did not alter body fat distribution. Total body fat, android fat and gynoid fat were positively related to smoking habit, and android fat was also positively related to waist circumference. Taken together, early postmenopause can be considered a time window of opportunity for preventing ailments such as atherogenic profile, obesity, increased cardiovascular risk and osteoporosis.


Analysis of Drug-Drug Interaction Labeling Language and Clinical Recommendations for Newly Approved Drugs Evaluated With Digoxin, Midazolam, and S-Warfarin.
To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations. This analysis aimed to assess the consistency in DDI labeling language in New Drug Applications (NDAs). NDAs of recently approved drugs (2012-2020) that increase the exposure of digoxin, midazolam, and S-warfarin, index substrates of P-glycoprotein, cytochrome P450 (CYP) 3A, and CYP2C9 activity, respectively, were fully reviewed. Noninhibitors were also evaluated to appreciate the extent of mechanistic extrapolation in case of negative index studies. After a systematic review of the DDI studies available in NDAs, FDA-approved labeling, and commonly used clinical tertiary resources, differences in DDI results presentation and resulting clinical recommendations were found, even for inhibitors that affect similarly the exposure of the same index substrate. Studies with negative results were often reported in the labels without providing mechanistic interpretation, thus limiting the possible extrapolation of this information to other known substrates. The variability in language affects how the information was presented to clinicians in tertiary resources. Strategies that aim to improve the translation of mechanistic DDI index studies into consistent labeling recommendations are briefly discussed in this review.


Biosorption of heavy metals: Transferability between batch and column studies.
The design of an industrial water treatment system using sorption is based on laboratory column tests. To verify the applicability of a column sorption system at industrial scale, it is necessary to determine the system's breakthrough time (BT) in a laboratory setting. In a laboratory column set-up, BT is referred to as the time taken by the adsorbate to appear at column outlet for the first time. This is when the mass transfer zone (MTZ), where the equilibrium sorption occurs, reaches the end of the sorbent bed. However, such laboratory set-up requires significant resources including laboratory space, time and multiple trials, which is the opposite to the batch experimental approach that is commonly used to assess efficiency of sorbents. This study identified batch sorption parameters that can be used to determine BT for a column sorption setting for three toxic heavy metals commonly found in industrial wastewater, namely, Pb2+, Cd2+ and Cu2+. The study conducted a comprehensive evaluation of the relationships between column BT and its key influential factors, namely, equilibrium sorption capacity (qe), pseudo second-order kinetic rate constant (k2) and initial sorption rate (h). The results revealed that BT can be better estimated using h compared to qe and k2. As such, a batch experiment which is more resource efficient could be undertaken for an initial estimation of the experimental BT of a column system. Moreover, a simulation model developed to replicate column sorption could demonstrate the behaviour of the breakthrough curve, which is a key to the selection and assessment of the performance of a sorbent in an adsorbent column. The estimation errors in qe and k2 were found to influence the simulation outcomes. Hence, it is necessary to further investigate the other factors that can potentially influence sorption behaviour.


Surgical and Radiology Trainees' Proficiency in Reading Mammograms: the Importance of Education for Cancer Localisation.
Medical imaging with mammography plays a very important role in screening and diagnosis of breast cancer, Australia's most common female cancer. The visualisation of cancers on mammograms often forms a diagnosis and guidance for radiologists and breast surgeons, and education platforms that provide real cases in a simulated testing environment have been shown to improve observer performance for radiologists. This study reports on the performance of surgical and radiology trainees in locating breast cancers. An enriched test set of 20 mammography cases (6 cancer and 14 cancer free) was created, and 18 surgical trainees and 32 radiology trainees reviewed the cases via the Breast Screen Reader Assessment Strategy (BREAST) platform and marked any lesions identifiable. Further analysis of performance with high- and low-density cases was undertaken, and standard metrics including sensitivity and specificity. Radiology trainees performed significantly better than surgical trainees in terms of specificity (0.72 vs. 0.35; P < 0.01). No significant differences were observed between the surgical and radiology trainees in sensitivity or lesion sensitivity. Mixed results were obtained with participants regarding breast density, with higher density cases generally having lower performance. The higher specificity of the radiology trainees compared to the surgical trainees likely represents less exposure to negative mammography cases. The use of high-fidelity simulated self-test environments like BREAST is able to benchmark, understand and build strategies for improving cancer education in a safe environment, including identifying challenging scenarios like breast density for enhanced training.


Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats.
Pulmonary artery hypertension (PAH) is characterized by vascular remodeling, high pulmonary blood pressure, and right ventricular hypertrophy. Oxidative stress, inflammation and pulmonary artery remodeling are important components in PAH. Ellagic acid (EA) is a phenolic compound with anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to investigate whether EA could prevent the development of monocrotaline (MCT)-induced PAH in rats. Male Sprague-Dawley rats received EA (30 and 50mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis. MCT induced PAH, oxidative stress, and NLRP3 inflammasome activation in vehicle-treated rats. EA reduced the right ventricle systolic pressure, the right ventricular hypertrophy and the wall thickness/external diameter ratio of the pulmonary arteries compared with vehicle. EA also inhibited the MCT-induced elevation of oxidative stress, NLRP3, and caspase-1, IL-β in the lungs and the elevated levels of brain natriuretic peptide (BNP) and inflammatory cytokines in serum. Ellagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.


Anti-tumour necrosis factor-alpha treatment for perianal Crohn's disease in Australia.
To examine the prevalence of perianal Crohn's disease (PCD) and the eligibility of PCD patients to access anti-tumour necrosis factor-alpha (anti-TNFalpha) treatment under current Australian Pharmaceutical Benefits Scheme (PBS) guidelines. A retrospective study of patients with Crohn's disease (CD) and PCD attending four large adult inflammatory bowel disease (IBD) centres in Australia between January 2004 and May 2008. Patients for whom anti-TNFalpha therapy was clinically indicated were assessed to determine whether they satisfied PBS criteria for subsidised medication. Prevalence of CD and PCD in patients attending different IBD centres; eligibility of PCD patients for PBS-subsidised anti-TNFalpha medication. Data were available on 3589 patients, representing about 6% of all patients with IBD in Australia. Of the 1815 patients with CD, 310 (17%) had PCD. Anti-TNFalpha therapy was deemed clinically indicated for 166 patients with PCD (54%), of whom 49 (30%) did not qualify for PBS-funded therapy. Thirty per cent of patients with clinically significant PCD currently do not have access to PBS-subsidised optimal medical treatment. We believe that PBS criteria should be extended to include this subgroup of IBD patients.


One hand cannot clap-a study of Arab practitioners of traditional and complementary medicine in Israel: identifying barriers to integrative oncology care.
The integration of complementary medicine is gradually becoming an accepted part of standard care for patients with cancer. In our integrative oncology program, we have encountered difficulties in recruiting Arab patients. In order to understand the special needs of this population, we conducted interviews among Arab practitioners of complementary and traditional medicine (CTM). The characteristics of practitioners and their views regarding the therapeutic process were examined. Semi-structured qualitative interviews were administered to 27 Arab practitioners of CTM whose clientele was comprised primarily of Arab cancer patients. Conventional content analysis of the transcribed interviews and field notes was performed in order to identify key themes. Three groups of CTM practice were identified: Folk-herbal medicine (n = 9), complementary medicine (CM; n = 14), and religious healing (n = 4). Seven factors were identified in the practitioner accounts: the duration and scheduling of treatment sessions, the language of communication, the presence of family members, the appearance of the practitioner, the definition of treatment goals, the discussion of behavioral and lifestyle changes, and finally, the use of tangible elements in treatment. The study of Arab CTM practitioner recommendations may help facilitate a culture-sensitive encounter with Arab patients with cancer. This approach may also have implications for other ethno-culturally unique populations.


Incidence and Predictors of Infections and All-Cause Death in Patients with Cardiac Implantable Electronic Devices: The Italian Nationwide RI-AIAC Registry.
The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. A total of 2675 patients (64.3% male, age 78 (70-84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38-12.08) and diabetes (OR: 2.22, 95% CI: 1.02-4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60-3.55 for each point), with a c-index = 0.64 (0.52-0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63-0.71) p < 0.001. In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.


Effects of a Cereal Bar with a Combination of Phytoestrogens on the Climacteric Symptoms: A Placebo-Controlled, Randomized Trial.
This study evaluated whether the consumption of a cereal bar combining different phytoestrogens could contribute to the reduction of climacteric symptoms in women. This is a clinical, prospective, randomized, simple-blind trial. Forty-eight women, aged 40-65 years, with climacteric symptoms, from a city in southwestern Paraná, Brazil. Participants were randomly assigned into two groups; Phytoestrogens group (PHY = 24), which received for 90-day period a cereal bar containing 80.73 milligrams of soybean and flaxseed phytoestrogens, and the placebo group (PLA = 24), which consumed rice flakes biscuit. Clinical, sociodemographic and anthropometric data were collected and climacteric symptoms were assessed using the Kupperman Index (KI). Forty-three women were analyzed (PHY = 21 and PLA = 22). There were significant reductions in the overall KI score in both groups at the end of the intervention period (p < 0.05). However, the comparison between the groups using linear regression models presented expressively better symptom improvement in the PHY group -6.43 over time (95% CI: -11.6; -1.26; p < 0.05) KI points, with perimenopausal -15.15 (95% CI: -28.95; -1.35) and postmenopausal women -19.34 (95% CI: -33.68; -4.99) showed considerably greater reductions in symptoms at the end of the intervention period compared to premenopausal women. There was also significant reduction in symptoms of hot flushes, paresthesia, sexual complaints, insomnia and melancholy. The consumption of a cereal bar containing phytoestrogens was able to improve the symptoms of climacteric syndrome.


Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation.
10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate to tetrahydrofolate (THF). Expression of the enzyme in FDH-deficient cancer cells induces cytotoxicity that can be reversed by supplementation with high concentrations of a reduced folate, 5-formyl-THF (leucovorin). In contrast, non-tumor cells are resistant to FDH. The present study was undertaken to investigate mechanisms that could protect cells against FDH suppressor effects. Using 10 microM leucovorin supplementation of FDH-sensitive A549 cells transfected for FDH expression, we selected clones that have acquired resistance against FDH. Resistant cells expressed high levels of FDH and were capable of growing after withdrawal of leucovorin. These cells, however, have increased doubling time due to prolonged S phase. They also have significantly increased levels of total folate pool and THF/5,10-methylene-THF pool while the level of 10-formyl-THF was two-fold lower than in parental FDH-sensitive cells. We have shown that the FDH-catalyzed reaction proceeds at about a three-fold slower rate at the ratio of 10-formyl-THF/THF corresponding to the resistant cells than at the ratio corresponding to parental sensitive cells, due to product inhibition (KI is 2.35 microM). FDH-resistant cells have strongly up-regulated dihydrofolate reductase (DHFR) that is proposed to be a mechanism for the alteration of folate pools and a key component of the acquired resistance. Elevation of DHFR in A549 cells by transient transfection decreased sensitivity to FDH toxicity and allowed selection of FDH-resistant clones. DHFR-induced repression of FDH catalysis could be an S phase-related metabolic adjustment that provides protection against FDH suppressor effects.


Ptychopteridae, a family of flies (Diptera) new to the Philippine Islands with the description of a new species.
Ptychoptera (Ptychoptera) noonadani sp. nov. is described and is the first record of family Ptychopteridae from the Philippine Islands. A key to males of all Ptychoptera species recorded from the Malay archipelago is presented.


Ophthalmic Delivery of Riboflavin Loaded Nanoparticulate Suspension in Keratoconus: A Preclinical Study in Rabbit Model.
The present investigation undertakes the formulation of nanoparticulate suspension of Riboflavin to treat keratoconus disease by applying it to the infected mice corneas. The nanoparticles of Riboflavin were prepared using single solvent evaporation method and later formulated as suspension using continuous probe sonication method. Then, both riboflavin nanoparticles and suspension were evaluated for various parameters. The nanoparticles showed smooth and spherical surface with in vitro drug release up to 77.89%. The drug content was found to be 97.23%-98.89%. The suspension was found to be visually clear with pH ranging from 6 to 7. The drug entrapment was found to be from 76.37% to 97.34%. Since there was no hemolytic activity, this formulation was suitable for ophthalmic administration. The Draize test confirmed the non-irritant, non-itchy nature of formulation. The prepared formulations, such as nanoparticulate gel and suspension, were found to be significantly efficacious in experimental animals.


The impact of donor selection on blood safety in Iran.
Donor selection is a critical process to identify high risk volunteers and defer them from donating blood. Despite viral screening test on all donated blood, one cannot rely on screening tests alone to ensure a safe blood supply. Monitoring and assessment of the deferral procedure is of utmost importance to balance blood availability and safety. This study compares the prevalence of HIV, HCV, and HBV markers between deferred donors and accepted blood donors in order to evaluate the effectiveness of the current donor selection process in Iran. This study was carried out on deferred blood donors throughout the country. A blood sample was collected from participants and tested for three viral markers: HbsAg, anti-HCV, and anti-HIV. Repeatedly reactive samples were retested with a confirmatory screening assay. The prevalence of viral markers among deferred donors was compared with national statistical data on blood donors. The prevalence of HIV, Hepatitis B, and Hepatitis C was 120 (CI 95%; 90-150), 1280 (CI 95%; 1170-1390), and 580 (CI 95%; 510-650) in 100,000 deferred donors respectively. A significant increase exists in the prevalence of HBV (1.7 times), HIV (24 times) and HCV (15 times) in deferred donors as compared to accepted blood donors. The effectiveness of donor selection in identifying high risk individuals is obvious upon comparing the prevalence of selected viral infections in deferred donors with those accepted for blood donation. This study showed the role and necessity of donor selection criteria.


[Carcinoma ex pleomorphic adenoma occurring in the sublingual gland: a case report].
Carcinoma ex pleomorphic adenoma occurring in the sublingual gland is extremely rare. In this report, a case of adenoid cystic carcinoma ex pleomorphic adenoma of the sublingual gland was presented.


The effect of inhibitors on the electron flow triggering photo-phobic reactions in Cyanophyceae.
1. Since photo-phobic reactions in the blue green alga Phormidium uncinatum seem to be triggered by changes of electron flow rates into or out of an electron pool situated in the electron transport chain between photo-system II and I, the effect of inhibitors affecting the electron transport chain has been studied. 2. Dose response curves of the phobic reaction have been measured by varying the trap energy in double beam light trap experiments with constant pairs of monochromatic light. From these dose response curves the effects of the inhibitors on both types of phobic reactions, i.e. exit reactions and entrance reactions, have been calculated. 3. Dibromothymoquinone (DBMIB) inhibits the electron transport between the electron pool and photosystem I by preventing the reoxidation of plastoquinone. The phobic entrance reaction, which results in an emptying of the light trap, is triggered by changes in the electron flow out of the pool; thus it is more effected by DBMIB than the exit reaction, which is mediated by the electron transport into the pool. 4. The phobic exit reaction, which results in accumulations in the light trap, is triggered by changes in the electron flow into the electron pool via photosystem II. 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) inhibits the electron transport near photosystem II; thus it affects the exit reaction more than the entrance reaction.


Biomechanical model registration for monitoring and simulating large orthodontic tooth movements in the maxilla and mandible.
Superimposition of digital dental-arch models allows quantification of orthodontic tooth movements (OTM). Currently, this procedure requires stable reference surfaces usually only present in the maxilla. This study aimed to investigate the accuracy of a novel superimposition approach based on biomechanical principles of OTM and the equilibrium of forces and moments (EFM)-applicable in both jaws-for monitoring and simulating large OTM. The study included 7 patients who had undergone extraction of the first (PM1-Ex) or second (PM2-Ex) premolar in each quadrant. Digital models taken at start and end of the T‑Loop treatment phase were superimposed by applying 3 EFM variants differing in the number of teeth used for registration. Maxillary OTM results for EFM were validated against those for a conventional surface registration method (SRM). In an additional case study, OTM were simulated for PM1-Ex, PM2-Ex and non-extraction treatment strategies. The EFM variant that included all teeth of the dental arch achieved the highest accuracy, with median translational and rotational OTM deviations from SRM of only 0.37 mm and 0.56°, respectively. On average, retracted canines and first premolars were distalized by 3.0 mm, accompanied by 6.2° distal crown tipping and 12.2° distorotation. The share of space closure by molar mesialization was 19.4% for PM1-Ex quadrants and 34.5% for PM2-Ex quadrants. EFM allows accurate OTM quantification relative to the maxillary and mandibular bases even in challenging situations involving large OTM. Superimposition of malocclusion and setup models enables realistic simulation of final tooth positions. This may greatly enhance the value of digital setups for decision-making in orthodontic treatment planning.


Repeat stereotactic body radiotherapy for oligometastatic disease.
Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit.


Influence of reduced concentration of L-glutamine on growth and viability of cells in monolayer, in spheroids, and in experimental tumours.
L-Glutamine is a requirement for many cells in tissue culture, an intermediate in many metabolic pathways, and an alternative substrate to glucose for energy metabolism. These properties suggest that glutamine concentration might be a determinant of cell viability in tumours, especially in regions that are deficient in other metabolites. We have therefore studied the effects of glutamine depletion on single cells in culture, on spheroids and on experimental tumours. Absence of glutamine suppressed the growth rate of two cell lines, but cells cultured for up to 6 h in the absence of glutamine had no decrease in plating efficiency. There was little effect on growth of MGH-U1 (human bladder cancer) spheroids of varying the glutamine concentration in the range of 0.1 to 2 mM and spheroids exposed to these concentrations did not develop central necrosis. Lower concentration of glutamine suppressed the rate of spheroid growth, and spheroids did not grow in the absence of glutamine. Pseudomonas 7A glutaminase reduced the survival of cells in glutamine-free culture and prevented growth of spheroids. Glutaminase was injected into mice bearing experimental tumours to reduce blood levels of glutamine; some animals also received 15 Gy radiation to their tumours to assess the effects of glutamine levels on surviving nutrient-deprived (i.e. hypoxic) cells. Glutaminase had no effect on cell survival in the Lewis lung tumour or in MGH-U1 xenografts, with or without radiation; glutaminase caused dose-dependent growth delay of the KHT tumour, which was additive to that caused by radiation. The present results suggest that (i) short-term changes of glutamine concentration have small effects on cell viability; and (ii) depletion of glutamine levels in blood through the in vivo use of glutaminase is unlikely to produce major therapeutic effects against nutrient-deprived cells in solid tumours.


Systems, variation, individuality and plant hormones.
Inter-individual variation in plants and particularly in hormone content, figures strongly in evolution and behaviour. Homo sapiens and Arabidopsis exhibit similar and substantial phenotypic and molecular variation. Whereas there is a very substantial degree of hormone variation in mankind, reports of inter-individual variation in plant hormone content are virtually absent but are likely to be as large if not larger than that in mankind. Reasons for this absence are discussed. Using an example of inter-individual variation in ethylene content in ripening, the article shows how biological time is compressed by hormones. It further resolves an old issue of very wide hormone dose response that result directly from negative regulation in hormone (and light) transduction. Negative regulation is used because of inter-individual variability in hormone synthesis, receptors and ancillary proteins, a consequence of substantial genomic and environmental variation. Somatic mosaics have been reported for several plant tissues and these too contribute to tissue variation and wide variation in hormone response. The article concludes by examining what variation exists in gravitropic responses. There are multiple sensing systems of gravity vectors and multiple routes towards curvature. These are an aspect of the need for reliability in both inter-individual variation and unpredictable environments. Plant hormone inter-individuality is a new area for research and is likely to change appreciation of the mechanisms that underpin individual behaviour.


A big encapsulated adrenal mass with well-circumscribed margin.
We present a case on adrenal schwannomas. The CT shows enhancement of distal adrenal gland lesion. We named it rabbit tail sign. Adrenal schwannomas are rare and presents a very small proportion of retroperitoneal schwannomas. It tends to be misdiagnosed because of lacking characteristics clinical presentations and CT features. And there is debate about its origination. The rabbit tail sign of distal adrenal gland is one typical radiographic feature of adrenal schwannomas. It also suggests the tumor may originate from dominate nerve of adrenal medulla.


Different ways of problematising biotechnology--and what it means for technology governance.
To understand controversies over technologies better, we propose the concept of 'problematisation'. Drawing on Foucault's idea of problematisation and on the concept of frames in media research, we identify characteristic forms of problematising biotechnology in pertaining controversies, typically emphasising ethical, risk or economic aspects. They provide a common basis for disputes and allow participants to argue effectively. The different forms are important for how controversies are negotiated, which experts get involved, what role public engagement plays and how political decisions are legitimized--in short, for technology governance. We develop a heuristic for analysing the link between forms of problematisation and different options for technology governance. Applied to synthetic biology, we discuss different problematisations of this technology and the implications for governance.


Identification of peptide sequences that target to the brain using in vivo phage display.
Phage display technology could provide a rapid means for the discovery of novel peptides. To find peptide ligands specific for the brain vascular receptors, we performed a modified phage display method. Phages were recovered from mice brain parenchyma after administrated with a random 7-mer peptide library intravenously. A longer circulation time was arranged according to the biodistributive brain/blood ratios of phage particles. Following sequential rounds of isolation, a number of phages were sequenced and a peptide sequence (CTSTSAPYC, denoted as PepC7) was identified. Clone 7-1, which encodes PepC7, exhibited translocation efficiency about 41-fold higher than the random library phage. Immunofluorescence analysis revealed that Clone 7-1 had a significant superiority on transport efficiency into the brain compared with native M13 phage. Clone 7-1 was inhibited from homing to the brain in a dose-dependent fashion when cyclic peptides of the same sequence were present in a competition assay. Interestingly, the linear peptide (ATSTSAPYA, Pep7) and a scrambled control peptide PepSC7 (CSPATSYTC) did not compete with the phage at the same tested concentration (0.2-200 pg). Labeled by Cy5.5, PepC7 exhibited significant brain-targeting capability in in vivo optical imaging analysis. The cyclic conformation of PepC7 formed by disulfide bond, and the correct structure itself play a critical role in maintaining the selectivity and affinity for the brain. In conclusion, PepC7 is a promising brain-target motif never been reported before and it could be applied to targeted drug delivery into the brain.


Synthesis and antiphytoviral activity of α-aminophosphonates containing 3, 5-diphenyl-2-isoxazoline as potential papaya ringspot virus inhibitors.
α-Aminophosphonates compounds containing 3,5-diphenyl-2-isoxazoline were synthesized and evaluated for their bioactivity. Seventeen of them showed good bioactivity (protection effect > 50%) in vivo against papaya ringspot virus, while two of them (V29 and V45) exhibited excellent antiviral activity (both 77.8%). In the latter case, the antiviral activity was close to that of antiphytovirucides ningnanmycin and dufulin (both 83.3%) at 500 mg/L. The preliminary structure-activity relationships indicated that the bioactivity was strongly influenced by the substituents.


Effects of elevated sulfate in eutrophic waters on the internal phosphate release under oxic conditions across the sediment-water interface.
Eutrophication in freshwater environments may be enhanced by the elevation of sulfate in waters, through the release of internal phosphorus (P) from anoxic sediments. However, the influence of increasing but modest sulfate concentrations (less than 3000 μM) on P release under oxic conditions across the sediment-water interface (SWI) in eutrophic freshwater is poorly understood. In this study, the profiles of P, iron (Fe), sulfur (S) and physicochemical parameters were measured in a simulated lacustrine system with varying concentrations of sulfate (970-2600 μM) in overlying water. The results indicated that elevated concentrations of sulfate increased the soluble reactive P in overlying waters under oxic conditions across the SWI. A 100 μM increase of sulfate was found to induce a 0.128 mgm-2d-1 increase of P flux from surface sediments into overlying waters under oxic conditions. Higher sulfate concentrations in the overlying waters increased the concentrations of labile S(-II) in the deep sediments, due to sulfate penetration and subsequent reduction to S(-II). We also found the fluxes of labile Fe (10.34 to 18.33 mgm-2d-1) and P (2.70 to 1.33 mgm-2d-1) from deep to surface sediment were both positive and greater than the corresponding fluxes (Fe, 2.2 to 3.51 and P, 2.6 to 0.39 mgm-2d-1, respectively) from surface sediment to the overlying water, suggesting that reduction of P-bearing Fe(III)(oxyhydr)oxides in deep anoxic sediment acted as a major source of internal P release. In addition, the upward flux of Fe(II) was significantly lower under higher sulfate conditions, indicating that the Fe(II) flux could be mitigated by formation of Fe(II) sulfides in the deep sediment. Under these conditions, less Fe(II) from deep sediments could be re-oxidized and combine with P in the surface, oxic sediment, thereby reducing the retention capacity for P and leading to higher release of internal P to the water column.


Impact of the COVID-19 pandemic on management and outcomes in acute appendicitis: Should these new practices be the norm?
In early 2020, the COVID-19 pandemic significantly altered management of surgical patients globally. International guidelines recommended that non-operative management be implemented wherever possible (e.g. in proven uncomplicated appendicitis) to reduce pressure on healthcare services and reduce risk of peri-operative viral transmission. We sought to compare our management and outcomes of appendicitis during lockdown vs a non-pandemic period. All presentations to our department with a clinical diagnosis of acute appendicitis between 12/03/2020 and 30/06/2020 were compared to the same 110-day period in 2019. Quantity and severity of presentations, use of radiological investigations, rate of operative intervention and histopathological findings were variables collected for comparison. There was a reduction in appendicitis presentations (from 74 to 56 cases), and an increase in radiological imaging (from 70.27% to 89.29%) (P = 0.007) from 2019 to 2020. In 2019, 93.24% of patients had appendicectomy, compared to 71.42% in 2020(P < 0.001). This decrease was most pronounced in uncomplicated cases, whose operative rates dropped from 90.32% to 62.5% (P = 0.009). Post-operative histology confirmed appendicitis in 73.9% in 2019, compared to 97.5% in 2020 (P = 0.001). Normal appendiceal pathology was reported for 17 cases (24.64%) in 2019, compared to none in 2020 (P < 0.001) - a 0% negative appendicectomy rate (NAR). The 0% NAR in 2020 is due to a combination of increased CT imaging, a higher threshold to operate, and is impacted by increased disease severity due to delayed patient presentation. This study adds to growing literature promoting routine use of radiological imaging to confirm appendicitis diagnosis. As we enter a second lockdown, patients should be encouraged to avoid late presentations, and surgical departments should continue using radiological imaging more liberally in guiding appendicitis management.


A magnetic resonance imaging study of hippocampal, amygdala and subgenual prefrontal cortex volumes in major depression subtypes: melancholic versus psychotic depression.
Volumetric studies examining brain structure in depression subtypes are limited and inconclusive. The aim of the current study was to compare the volumes of brain regions previously implicated in depression among patients with melancholic major depressive disorder (MDD), patients with psychotic MDD and normal controls. Twenty two patients with melancholic MDD, 17 with psychotic MDD and 18 normal controls were included in the study. Hippocampal (HV), amygdala (AV), anterior (ASCV) and posterior (PSCV) subgenual cortex volumes were measured on magnetic resonance volumetric images. There were no volumetric differences between patients with melancholic and psychotic subgroups. We identified larger AVs and smaller left ASCVs in both patient groups compared to controls with medium to large effect sizes. Regression analysis revealed that AVs were predicted by the presence of depression, late depression-onset, insomnia and left hippocampal tail volume in patients, but not in controls. There were no differences in HVs, right ASCVs and PSCVs across the 3 groups. Small sample size, a possible inclusion of paracingulate gyrus in ASCV and PSCV tracings, significant differences in education level and medication status are discussed as limitations. Diagnostically delineated melancholic and psychotic MDD patients do not differ in medial temporal and cingulate volumes. However, significant volumetric differences were detected between both patient-groups and controls.


Studies on the frequency and associations of islet-cell antibodies in juvenile diabetes mellitus.
Ninety-six juvenile onset type diabetics showed an increase in the frequency of HLA B8 and B15 and a decrease in frequency of HLA B7 antigens. Sixty-four maturity onset diabetics showed no disturbance in the frequency of these antigens. Fifty-four of the juvenile onset type diabetics, with an average duration of disease of 3.2 years were tested for the presence of islet cell antibodies (ICAs). Thirty-two percent were positive, the frequency decreasing from 70% in those patients tested within one year of diagnosis to 0.5% in those patients tested more than 5 years after diagnosis. No correlation was found between HLA type and the frequency of ICAs, but there was an increase in other autoantibodies in B15 positive patients. Preliminary absorption studies suggest a cross reactivity of ICAs and Coxsackie B4 virus.


Does surgical approach matter in the treatment of pediatric ulcerative colitis?
This study aims to compare the morbidity of open versus laparoscopic colectomy or proctocolectomy for pediatric patients with ulcerative colitis (UC) using national readmission outcomes. The 2010-2014 Nationwide Readmissions Database was used to identify patients < 18 years (excluding newborns) who underwent colectomy or proctocolectomy for UC. Patients with planned readmissions for staged procedures were excluded from readmission analysis. Demographics, hospital factors, and outcomes were compared by operative approach (open vs. laparoscopic) using standard statistical analysis. Results were weighted for national estimates. There were 1922 patients (51% female, age 13 ± 3 years) with UC who underwent colectomy or proctocolectomy during index admission. Most cases were performed open (54%) and as elective admissions (64%). Compared to open approach, laparoscopy was associated with shorter index hospital length of stay (8 [5-17] days vs. 9 [6-18] days, p = 0.015), fewer surgical site infections (< 2% vs. 2%, p = 0.022), and less post-operative gastrointestinal dysfunction (5% vs. 8%, p = 0.008). After stratifying to control for elective and unplanned index admissions, laparoscopic approach was associated with fewer small bowel obstructions during index hospitalizations in both elective (9% vs. 15%, p = 0.003) and unplanned (5% vs. 16%, p<0.001) settings. Readmission for surgical site infection was also less common following laparoscopic approach in both elective (0% vs. 7%, p = 0.008) and unplanned (0% vs. < 7%, p = 0.017) settings. In pediatric patients with ulcerative colitis, laparoscopic colectomy or proctocolectomy is associated with shorter hospital length of stay, less post-operative complications, and improved readmission outcomes.


Synergy Effect of a π-Conjugated Ionic Compound: Dual Interfacial Energy Level Regulation and Passivation to Promote Voc and Stability of Planar Perovskite Solar Cells.
Defects and energy offsets at the bulk and heterojunction interfaces of perovskite are detrimental to the efficiency and stability of perovskite solar cells (PSCs). Herein, we designed an amphiphilic π-conjugated ionic compound (QAPyBF4 ), implementing simultaneous defects passivation and interface energy level alignments. The p-type conjugated cations passivated the surface trap states and optimized energy alignment at the perovskite/hole transport layer. The highly electronegative [BF4 ]- enriched at the SnO2 interface featured desired band alignment due to the dipole moment of this interlayer. The planar n-i-p PSC had an efficiency of 23.1 % with Voc of 1.2 V. Notably, the synergy effect elevated the intrinsic endothermic decomposition temperature of the perovskite. The modified devices showed excellent long-term thermal (85 °C) and operational stability at the maximum power point for 1000 h at 45 °C under continuous one-sun illumination with no appreciable efficiency loss.


Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences?
Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.


Astragaloside regulates lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis to inhibit the proliferation of fibroblast‑like synoviocytes in rats with rheumatoid arthritis.
Previous studies have confirmed that astragaloside (AST) exerts a positive effect on alleviating synovial and joint injury in rheumatoid arthritis (RA). However, the precise mechanisms through which AST acts in the treatment of RA remain unclear. Long non‑coding RNA (lncRNA) LOC100912373 was identified as a key gene related to RA and has been proven to interact with miR‑17‑5p, in order to regulate the pyruvate dehydrogenase kinase 1 and protein kinase B axis (PDK1/AKT axis). The present study aimed to determine whether AST may treat RA through the interaction between lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis. MTT assays and flow cytometry were used to detect the proliferation and cell cycle progression of AST‑treated fibroblast‑like synoviocytes (FLSs). The expression of lncRNA LOC100912373 and miR‑17‑5p, as well as relative the mRNA expression of the PDK1 and AKT genes following AST intervention was detected by reverse transcription‑quantitative PCR (RT‑qPCR), immunofluorescence and western blot analysis. The results revealed that AST inhibited FLS proliferation, reduced lncRNA LOC100912373 expression levels, increased miR‑17‑5p expression levels, and decreased the PDK1 and p‑AKT expression levels. Additionally, consecutive rescue experiments revealed that AST counteracted the effects of lncRNA LOC100912373 overexpression on FLS proliferation and cell cycle progression. On the whole, the present study demonstrates that AST inhibits FLS proliferation by regulating the expression of lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis.


Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.
Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.


Dephosphorylation of 19K and 21K polypeptides in response to thyroid-stimulating hormone in cultured thyroid cells.
Cultured dog thyroid cells incubated with [32P] phosphate contain at least two phosphoproteins of 19 and 21 kDalton (K), as determined by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Myosin light chain appears to be a component of the 19K and 21K phosphoproteins by the following criteria: 1) coextraction with myosin heavy chain from Triton-insoluble cytoskeletons with KCl-ATP, 2) coisolation with myosin heavy chain by immunoprecipitation, and 3) purification of undenatured myosin with pyrophosphate-agarose gel electrophoresis. The phosphorylation state of these proteins is decreased by incubation of cells with TSH. In the basal state, the 19K and 21K proteins from Triton-insoluble cytoskeleton fractions contain 0.86 +/- 0.07 (+/- SE) mol phosphate/mol protein, which is reduced to 0.34 +/- 0.03 in TSH-treated cells. TSH-induced dephosphorylation occurs in 1 min with 2.5 mU/ml TSH and reaches a maximum at 15 min. This TSH effect appears to be mediated by cAMP, since it is mimicked by (Bu)2cAMP, forskolin, cholera toxin, and prostaglandin E1 and is potentiated by isobutylmethylxanthine. Carbamylcholine, ionophore A23187, and norepinephrine, which inhibit TSH stimulation of cAMP, have no effect on basal phosphorylation of the 19K and 21K proteins, but do inhibit the effect of TSH.


Novel and simple approach using synthesized nickel nanoparticles to control blood-sucking parasites.
The present study was on assessment of the anti-parasitic activities of nickel nanoparticles (Ni NPs) against the larvae of cattle ticks Rhipicephalus (Boophilus) microplus and Hyalomma anatolicum (a.) anatolicum (Acari: Ixodidae), fourth instar larvae of Anopheles subpictus, Culex quinquefasciatus and Culex gelidus (Diptera: Culicidae). The metallic Ni NPs were synthesized by polyol process from Ni-hydrazine as precursor and Tween 80 as both the medium and the stabilizing reagent. The synthesized Ni NPs were characterized by Fourier transform infrared (FTIR) spectroscopy analysis which indicated the presence of Ni NPs. Synthesized Ni NPs showed the X-ray diffraction (XRD) peaks at 42.76°, 53.40°, and 76.44°, identified as 111, 220, and 200 reflections, respectively. Scanning electron microscopy (SEM) analysis of the synthesized Ni NPs clearly showed that the Ni NPs were spherical in shape with an average size of 150 nm. The Ni NPs showed maximum activity against the larvae of R. (B.) microplus, H. a. anatolicum, A. subpictus, C. quinquefasciatus and C. gelidus with LC(50) values of 10.17, 10.81, 4.93, 5.56 and 4.94 mg/L; r(2) values of 0.990, 0.993, 0.992, 0.950 and 0.988 and the efficacy of Ni-hydrazine complexes showed the LC(50) values of 20.35, 22.72, 8.29, 9.69 and 7.83 mg/L; r(2) values of 0.988, 0.986, 0.989, 0.944 and 0.978, respectively. The findings revealed that synthesized Ni NPs possess excellent larvicidal parasitic activity. To the best of our knowledge, this is the first report on larvicidal activity of blood feeding parasites using synthesized Ni NPs.


Erratum: Inhibition and Removal of Mature Mixed-Bacteria Biofilms on Voice Prostheses by Sodium Selenite [Corrigendum].
[This corrects the article DOI: 10.2147/IDR.S393434.].


Objective assessment of a surgical trainee.
Early assessment of surgical trainees in their training programme is essential. A strong subjective observer's bias occurs when using the mentor assessment form. In-service examinations and qualifying examinations are only valid measurements of the trainee's knowledge of factual material. An objective method to assess a surgical trainee's clinical performance is introduced in the present study. We examined the Generalized Linear Mixed Model statistical methodology to obtain standardized performance scores that would identify good and poor performers while taking into account the effects of patients' risk factors. Data regarding the postappendectomy complication occurrence and operation duration were retrospectively collected for each trainee. These variables were analysed by applying logistic regression and proportional hazards regression models respectively. Standardized trainee scores were obtained as by-products that measured the residual effect of surgeons' performances after taking into account the effects of possible risk factors. A total of 37 trainees were involved in 638 appendectomy operations from 1994 to 1997. Age, concurrent medical disease and presence of pus were significant risk factors associated with complication occurrence. Concurrent medical disease, presence of pus, operative findings of gangrenous or ruptured appendix as well as the experience of the surgeon had a significant effect on the operation duration. The present study identifies four trainees that displayed good clinical performance, and one trainee that displayed poor clinical performance of appendectomy. Our proposed method makes use of recently developed statistical methodology for predicting the effect of surgeons' performance,taking into account variations in their case-mix and their patients' fitness. This approach may serve as a very powerful tool for early assessment of a trainee's clinical proficiency, and may also have implications for the future assessment of a surgeon's clinical standard.