Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive.
Microcephaly is a genetically heterogeneous disorder and is one of the frequently notable conditions in paediatric neuropathology which exists either as a single entity or in association with other co-morbidities. More than a single gene is implicated in true microcephaly and the list is growing with the recent advancements in sequencing technologies. Using massive parallel sequencing, we identified a novel frame shift insertion in the abnormal spindle-like microcephaly-associated protein gene in a client with true autosomal recessive primary microcephaly. Exome sequencing in the present case helped in identifying the true cause behind the disease, which helps in the premarital counselling for the sibling to avoid future recurrence of the disorder in the family.


The pattern and distribution of malignancies reported in Hadramout, Yemen--2006.
To describe the pattern of malignancies among all patients with cancer recorded in Hadramout (East of Yemen) in 2006, and to explore the association with age, sex, and site of cancer. A retrospective descriptive study of all registered cancers (334) was carried out. Efforts were made to avoid case duplication. The neoplasms had been classified according to international classification of diseases for oncology. The cancers were more frequent in females (55%) than males (45%). The three most affected sites were digestive organs (20.35%), breast (14.37%), and haematopoietic system (11.98%). In the paediatric group, haematopoietic system (leukaemia) was most common. Digestive organs in general, with breast in females, were the most frequent sites of malignancies. Colorectal cancers were the most common cancers in digestive organs.


Molecular mechanisms of Huanglian jiedu decoction on ulcerative colitis based on network pharmacology and molecular docking.
Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC using network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are very important to the PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had a good binding ability with the Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.


Echographic and physical characterization of albumin-stabilized nanobubbles.
There has been increasing interest in using nanobubbles (NBs) for ultrasound mediated drug delivery as well as for ultrasound imaging. Albumin NBs are especially attractive for its potential of becoming a versatile platform for drug carriers and molecular targeted therapy agents. However, physical characterization of NBs is generally considered to be difficult due to various technical issues, such as concentration limitations, nanoparticle contamination, etc. In the present study, we measured the size distribution, concentration and weight density of albumin stabilized NBs by means of multiple nanoscale measurement modalities. Laser nanoparticle tracking analysis, multicolor flow cytometry, resonance mass evaluation showed consistent measurement results of the NBs with low mass weight density and diameter size ranging from 100 nm to 400 nm. Furthermore, the NB solution showed excellent images by high frequency ultrasound (30-50 MHz) in flow model acoustic phantoms. The NBs also induced acute cell disruption by low intensity ultrasound (0.8 W/cm2) irradiation. We successfully fabricated and characterized albumin stabilized NBs which could serve as an effective platform for future theranositic agents.


Drosophila microRNA modulates viral replication by targeting a homologue of mammalian cJun.
MicroRNAs (miRNAs) are important regulators of biological processes, including host-virus interaction. This study investigated the involvement of Drosophila melanogaster miR-8-5p in host-virus interaction. Drosophila flies and cells challenged with Drosophila C virus (DCV) were found to have lower miR-8-5p abundance compared to uninfected samples. Lowering miR-8-5p abundance by experimental inhibition of the miRNA led to an increase in viral accumulation, suggesting that the observed decrease in the miR-8-5p abundance during DCV infection enhances viral replication. miR-8-5p putative targets were identified and included dJun, a transcription factor gene whose mammalian homologue cJun is induced by various viruses through kinase activation. Increasing miR-8-5p abundance using miR-8-5p mimics resulted in a decrease in dJun and GFP reporter levels. Furthermore, when the putative target in dJun was mutated, addition of miR-8-5p mimics did not result in the same antagonistic effect on dJun. These results show negative regulation of dJun by miR-8-5p and suggest that an miRNA-mediated pathway is involved in dJun regulation during viral infection. To analyse the role of dJun during DCV infection, dJun was knocked down in cells prior to DCV infection. Knockdown of dJun decreased DCV replication, providing evidence that dJun up-regulation that is concomitant with miR-8-5p down-regulation during DCV infection supports viral replication. These results highlight the role of miRNA in regulating the transcription factor gene dJun and uncover a previously unrecognized mechanism by which dJun is regulated during host-virus interaction.


In Vivo Rescue of the Hematopoietic Niche By Pluripotent Stem Cell Complementation of Defective Osteoblast Compartments.
Bone-forming osteoblasts play critical roles in supporting bone marrow hematopoiesis. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSC), are capable of differentiating into osteoblasts. To determine the capacity of stem cells needed to rescue aberrant skeletal development and bone marrow hematopoiesis in vivo, we used a skeletal complementation model. Mice deficient in Runx2, a master transcription factor for osteoblastogenesis, fail to form a mineralized skeleton and bone marrow. Wild-type (WT) green fluorescent protein (GFP)+ ESCs and yellow fluorescent protein (YFP)+ iPSCs were introduced into Runx2-null blastocyst-stage embryos. We assessed GFP/YFP+ cell contribution by whole-mount fluorescence and histological analysis and found that the proportion of PSCs in the resulting chimeric embryos is directly correlated with the degree of mineralization in the skull. Moreover, PSC contribution to long bones successfully restored bone marrow hematopoiesis. We validated this finding in a separate model with diphtheria toxin A-mediated ablation of hypertrophic chondrocytes and osteoblasts. Remarkably, chimeric embryos harboring as little as 37.5% WT PSCs revealed grossly normal skeletal morphology, suggesting a near-complete rescue of skeletogenesis. In summary, we demonstrate that fractional contribution of PSCs in vivo is sufficient to complement and reconstitute an osteoblast-deficient skeleton and hematopoietic marrow. Further investigation using genetically modified PSCs with conditional loss of gene function in osteoblasts will enable us to address the specific roles of signaling mediators to regulate bone formation and hematopoietic niches in vivo. Stem Cells 2017;35:2150-2159.


Phytochemical constituents of Inula britannica as potential inhibitors of dihydrofolate reductase: A strategic approach against shigellosis.
Shigella dysenteriae type 1 is considered as an epidemic in different developing countries, which is responsible for the most severe form of bacterial dysentery. It habitually can develop to the most severe form of dysentery with deadly complications. Development of drugs against this disease is still ongoing. Therefore, we used in silico studies to screen the Inula britannica phytocompounds that are used in traditional Chinese and Kampo Medicines and have activities against different diseases. Spinacetin, eupatin, chrysoeriol and diosmetin were successfully passed through the docking-based screening and absorption, distribution, metabolism, excretion and toxicity (ADMET) filtration. The estimated docking affinities of eupatin, diosmetin, chrysoeriol and spinacetin with Dihydrofolate reductase type 1 (DHFR-1), were -6.5, -6.5, -6.3 and -6.1 kcal/mol, respectively. Which were selected for further investigations based on their favorable ADME/Tox characteristics. Then, the 100 ns molecular dynamics (MD) simulations of apo DHFR, spinacetin-DHFR, eupatin-DHFR, chrysoeriol-DHFR and diosmetin-DHFR complexes were carried out. The RMSD fluctuations of the spinacetin, eupatin, chrysoeriol and diosmetin inside the binding site were explored. Subsequently, the effect of binding Spinacetin, eupatin, chrysoeriol and diosmetin upon the dynamic stability of protein was assessed. Additionally, Principal Component Analysis (PCA) and Hydrogen bond analysis was performed for the apo protein and the protein ligand complexes. The results revealed that chrysoeriol and eupatin has good inhibitory effects against DHFR-1 as treatment for Shigella dysenteriae type when compared to other compounds under study. Hence this study implies that eupatin and chrysoeriol are a significantly potential drug like molecule for the treatment of Shigellosis and must undergo validation through in vivo and in vitro experiments.Communicated by Ramaswamy H. Sarma.


Meaningful Transitions: Enhancing Clinician Roles in Transition Planning for Adolescents With Autism Spectrum Disorders.
Purpose The purpose of this tutorial is to provide speech-language pathologists (SLPs) with foundational information that will assist them in transition planning for students with autism spectrum disorder (ASD) based on a review of current literature. SLPs must be knowledgeable of transition planning in order to assist students with ASD and their families with preparing for their future. An appreciation and awareness of pertinent assessments, functional goals, and factors associated with successful postsecondary outcomes are essential competencies that SLPs need when planning for the transition process. SLPs are ideal workforce development partners. They facilitate independence, communication, and interaction skills necessary for postsecondary and workplace success. Speech-language services are one of the most common special education services received by high school students with Individualized Education Programs. However, SLPs receive little preparation on the specifics or nuances of transition planning prior to working in the educational settings, despite the high incidence of speech-language services in secondary education. Method This tutorial reviews and synthesizes research findings related to assessment planning, goal-setting, and Individualized Education Program implementation for achieving meaningful postsecondary transitions for students with ASD. Additionally, it highlights some of the key postsecondary skillsets related to speech-language therapy services, including the development of self-determination, self-advocacy, social competence, and adaptive behaviors. Conclusion Greater focus on higher quality transition planning requires SLPs to develop high levels of knowledge and competencies in the transition planning process. This tutorial educates clinicians on the unique challenges faced by individuals with ASD and provides evidence-based strategies to help students and families successfully plan for and navigate postsecondary transitions.


Molecular approaches to potentiate cisplatin responsiveness in carcinoma therapeutics.
Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.


Survey of peridomestic mosquito species of Jaffna peninsula in Sri Lanka.
Surveys of mosquitos in Sri Lanka have generally been confined to the South. A recent study in Jaffna peninsula in northern Sri Lanka reported on the biology of peridomestic mosquito species. The present survey indicates the predominant species to be Armigeres durhami (Edwaards) and Armigeres subalbatus (Coquillett). Aedes albopictus (Skuse), Ae. aegypti (Linnaeus) and Ae. novalbopictus Barraud were recorded only occasionally during the survey. Sampling of ponds in the Jaffna peninsula recorded the presence of Ae. aegypti, Anopheles sp. and Culex quinquefasciatus (Say).


Fever of unknown origin as the first presentation of candida vertebral osteomyelitis: A case report.
Candida osteomyelitis is a rare disorder; however, its incidence has drastically risen especially during the last 3 decades. Diagnosis is usually delayed due to nonspecific symptoms. Thus, its management would not be performed at the proper time, which leads to increased morbidity. The optimal management of candida osteomyelitis is not clearly defined but most recommendations advise prolonged antifungal therapy in addition to surgery. Here, we report candida osteomyelitis in a patient with a history of pancreatic adenocarcinoma that presented with prolonged FUO as her first presentation. Fortunately, her symptoms completely resolved after prolonged medical therapy despite delay diagnosis due to her unusual presentation. To the best of our knowledge, it is the first report of candida vertebra osteomyelitis that presents with prolonged FUO as the first presentation.


[Antineoplastic chemotherapy for cervical carcinoma (author's transl)].
The effectiveness of antineoplastic substances on cervical carcinoma is insufficient. While combined chemotherapy was found to be more effective than monotherapy, satisfactory results were not achieved either. When it comes to recurrent or metastatic cervical carcinoma, antineoplastic chemotherapy, therefore, is not recommended unless all surgical and radiotherapeutic means have been tried with no success. Benefit to the patient and expected molestation should be carefully weighed, before a decision is made.


Acoustic scattering by smooth elastic cylinders insonified by directional transceivers: Monostatic theory and experiments.
A theoretical model for predicting the acoustic field scattered by an elastic cylinder that is partially insonified by a directional transceiver is proposed in the form of a simple approximate one-dimensional integral. This model accounts for spherical spreading and directivity of the incident waves and extends the formulation used in a preceding article [Gurley and Stanton, J. Acoust. Soc. Am. 94, 2746-2755 (1993)] by including effects due to oblique insonification of a long cylinder assuming negligible end-contributions. The scattered field of an infinitely long cylinder for obliquely incident plane waves and point receivers is used to approximate the apparent volume flow of cylinders partially insonified by directional transceivers. The scattered pressure that is derived using the apparent volume flow, in contrast to the previous formulation, is capable of predicting axially propagating guided wave resonances; these natural modes are excited, in addition to circumferential ones, at off-normal incident angles. The model is compared with exact numerical simulations and with previously published as well as new laboratory data. The analysis illustrates the different realistic effects associated with scattering from elastic cylinders insonified by a directional transceiver both theoretically and experimentally.


The effect of adopting new storage methods for extending product validity periods on manufacturers expected inventory costs.
The validness of the expiration dates (validity period) that manufacturers provide on food product labels is a crucial food safety problem. Governments must study how to use their authority by implementing fair awards and punishments to prompt manufacturers into adopting rigorous considerations, such as the effect of adopting new storage methods for extending product validity periods on expected costs. Assuming that a manufacturer sells fresh food or drugs, this manufacturer must respond to current stochastic demands at each unit of time to determine the purchase amount of products for sale. If this decision maker is capable and an opportunity arises, new packaging methods (e.g., aluminum foil packaging, vacuum packaging, high-temperature sterilization after glass packaging, or packaging with various degrees of dryness) or storage methods (i.e., adding desiccants or various antioxidants) can be chosen to extend the validity periods of products. To minimize expected costs, this decision maker must be aware of the processing costs of new storage methods, inventory standards, inventory cycle lengths, and changes in relationships between factors such as stochastic demand functions in a cycle. Based on these changes in relationships, this study established a mathematical model as a basis for discussing the aforementioned topics.


Outcomes of laparoscopic single-incision caecal pole resection for low-grade appendiceal mucinous neoplasm.
Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disease, and its clinical course varies from an incidental finding without symptoms to pseudomyxoma peritonei. Furthermore, there are few established treatment guidelines. This study was designed to confirm the outcomes in patients diagnosed with LAMN who underwent single-incision laparoscopic caecal pole resection. This study was conducted on pathologically confirmed LAMNs from patients who underwent surgery at a single centre, a tertiary institution, from July 2016 to August 2022. Patients diagnosed with LAMN as a result of biopsy were included. All surgeries were performed with single-incision laparoscopic caecal pole resection by a single surgeon. A total of 70 patients were included. The median age was 65.5 years and 36 (51.4%) patients were female. The baseline carcinoembryonic antigen (CEA) was 8.08 ng/mL (0.76-148.11). The mean maximum diameter was 29.4 mm (7-70) and calcification was seen in 22 cases on pre-operative computed tomography (CT). As a result of histological examination, all patients were marginally negative. The larger the tumour size, the higher the CEA was (P = 0.011), and it was often accompanied by calcification (P = 0.021). In addition, tumour size and CEA showed a positive partial correlation with each other (r = 0.318, P = 0.018). The overall median follow-up period was 22.7 months (2-60). One case had suspected of recurrence on CT scan performed at 33 months following the surgery, but there were no related symptoms. Single-port laparoscopic caecal pole resection without margin involvement in LAMN was safe and feasible, and showed a favourable long-term outcome.


Just a drop of cement: a case of cervical spine bone aneurysmal cyst successfully treated by percutaneous injection of a small amount of polymethyl-methacrylate cement.
Aneurysmal bone cyst (ABC) is a benign hemorrhagic tumor, commonly revealed by local pain. The best treatment for this lesion is still controversial. We report the case of a patient with chronic neck pain revealing an ABC of the third cervical vertebra. After percutaneous injection of a small amount of polymethyl-methacrylate bone cement, the patient experienced significant clinical and radiological improvement.


Characteristics and factors associated with intraocular lens tilt and decentration after cataract surgery.
To analyze the characteristics and factors associated with intraocular lens (IOL) tilt and decentration after uneventful phacoemulsification with IOL implantation. Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Cross-sectional study. All patients underwent a general ophthalmologic examination and anterior segment photography. IOL tilt and decentration were measured with a second-generation anterior segment optical coherence tomography (Casia2). Univariate and multivariate regression analyses were performed to assess the association between IOL tilt and decentration with ocular biometric and systemic parameters, and the visual acuity. A total of 196 eyes of 196 patients were enrolled in this study. IOLs showed a mean tilt of 4.8 degrees toward the inferotemporal direction, and the mean decentration was 0.21 mm. Both eyes presented a mirror symmetry relationship. Twenty-two eyes (11.22%) had a tilt greater than 7 degrees, and 21 eyes (10.72%) had a decentration more than 0.4 mm. Multivariate regression analysis showed previous pars plana vitrectomy (PPV) and short axial length (AL) were associated with greater IOL tilt (P = .014 and P < .001). In addition, long AL, thicker lens, and less capsulorhexis-IOL overlap were positively correlated with decentration (P < .001, P = .029, and P = .026). Corrected distance visual acuity did not directly correlate with IOL tilt and decentration (P = .417 and P = .550). PPV history and short AL were associated with greater IOL tilt, whereas longer AL, thicker lens, and overlarge capsulorhexis contribute to greater decentration. Implantation of toric and multifocal IOLs in these patients should be cautious.


Cardiac allotransplantation across major blood group barriers in the baboon.
In heterotopic heart transplantation experiments in Chacma baboons, some of the animals were significantly immunosuppressed with cyclosporine, resulting in prolonged cardiac allograft survival. ABO blood group incompatibility between recipient and donor did not significantly influence mean allograft survival, but early hyperacute (vascular) or acute (cellular) rejection occurred only when ABO incompatibility was present.


Plague: Infections of Companion Animals and Opportunities for Intervention.
Plague is a zoonotic disease, normally circulating in rodent populations, transmitted to humans most commonly through the bite of an infected flea vector. Secondary infection of the lungs results in generation of infectious aerosols, which pose a significant hazard to close contacts. In enzootic areas, plague infections have been reported in owners and veterinarians who come into contact with infected pets. Dogs are relatively resistant, but can import infected fleas into the home. Cats are acutely susceptible, and can present a direct hazard to health. Reducing roaming and hunting behaviours, combined with flea control measures go some way to reducing the risk to humans. Various vaccine formulations have been developed which may be suitable to protect companion animals from contracting plague, and thus preventing onward transmission to man. Since transmission has resulted in a number of fatal cases of plague, the vaccination of domestic animals such as cats would seem a low cost strategy for reducing the risk of infection by this serious disease in enzootic regions.


Application of High-speed Super-resolution SPEED Microscopy in Live Primary Cilium.
The primary cilium is a microtubule-based protrusion on the surface of many eukaryotic cells and contains a unique complement of proteins that function critically in cell motility and signaling. Since cilia are incapable of synthesizing their own protein, nearly 200 unique ciliary proteins need to be trafficked between the cytosol and primary cilia. However, it is still a technical challenge to map three-dimensional (3D) locations of transport pathways for these proteins in live primary cilia due to the limitations of currently existing techniques. To conquer the challenge, recently we have developed and employed a high-speed virtual 3D super-resolution microscopy, termed single-point edge-excitation sub-diffraction (SPEED) microscopy, to determine the 3D spatial location of transport pathways for both cytosolic and membrane proteins in primary cilia of live cells. In this article, we will demonstrate the detailed setup of SPEED microscopy, the preparation of cells expressing fluorescence-protein-labeled ciliary proteins, the real-time single-molecule tracking of individual proteins in live cilium and the achievement of 3D spatial probability density maps of transport routes for ciliary proteins.


An Under-the-Table Leg-Movement Apparatus and Changes in Energy Expenditure.
Introduction: Deskwork contributes substantially to sedentariness. Here, we evaluated an under-the-table apparatus that was designed to promote leg movement (fidgeting) while seated. Our hypothesis was that the under-the-table apparatus would increase energy expenditure. Methods: We measured energy expenditure and heart rate in 26 people while they sat and worked using a standard chair, walked on a treadmill, and sat and worked using an under-the-desk apparatus that encouraged leg movement. Results: Energy expenditure increased significantly while using the under-the-table apparatus when compared to the standard office chair (standard chair, 81 ± 18 kcal/h; under-the-table apparatus, 96 ± 23 kcal/h) (P < 0.001); representing an 18 ± 16% increase. The changes in energy expenditure were not as great as walking (1 mph, 168 ± 46 kcal/h, P < 0.001; 2 mph, 205 ± 51 kcal/, P < 0.001), representing 107 ± 37% and 155 ± 48% increases over baseline, respectively. Conclusions: An under-the-table apparatus that promotes leg movement can increase energy expenditure by approximately 20%. Dynamic sitting is promoted by this apparatus and may be among a lexicon of options to help people move more while seated at work.


Acoustic factors affecting interaural level differences for cochlear-implant users.
Bilateral cochlear-implant (BICI) listeners primarily use interaural level differences (ILDs) to localize sound in the horizontal plane. However, the ILD magnitude is altered at different frequencies and azimuths due to a combination of several acoustic phenomena such as the acoustical bright spot, acoustic axis, and microphone porting. This paper investigated the effects of BICI microphone placement on ILDs through an analysis of head-related transfer functions. At-the-canal BICI microphone placement provided both larger and more monotonic ILD-azimuth functions than behind-the-ear microphone placement. Results have implications for the fitting of clinical devices and their effect on sound localization in BICI users.


Pattern formation in a monolayer of magnetic spheres.
Pattern formation is investigated for a vertically vibrated monolayer of magnetic spheres. The spheres of diameter D encase cylindrical magnetic cores of length l. For large D/l, we find that the particles form a hexagonal-close-packed pattern in which the particles' dipole vectors assume a macroscopic circulating vortical pattern. For smaller D/l, the particles form concentric rings. The static configurational magnetic energy (which depends on D/l) appears to be a determining factor in pattern selection even though the experimental system is driven and dissipative.


Heart failure accompanied by sick euthyroid syndrome and exercise training.
Sick euthyroid syndrome is defined as the decrease of serum free triiodothyronine with normal free L-thyroxin and thyrotropin. Its appearance in patients with chronic heart failure is an indicator of severity. Exercise training through a wide variety of mechanisms reverses sick euthyroid syndrome (normalization of free triiodothyronine levels) and improves the ability to exercise. There is a connection during exercise among dyspnea, hyperventilation, fatigue, catecholamines, a decrease in the number and function of beta-blocker receptors, and elevation of serum free triiodothyronine. It is not known whether sick euthyroid syndrome contributes to the development of heart failure or is only an attendant syndrome.


INVOLVING PARENTS IN A COMMUNITY-BASED, CULTURALLY-GROUNDED MENTAL HEALTH INTERVENTION FOR AMERICAN INDIAN YOUTH: PARENT PERSPECTIVES, CHALLENGES, AND RESULTS.
An important predictor of youth well-being and resilience is the presence of nurturing adults in a youth's life. Parents are ideally situated to fulfill this role but often face challenges and stressors that impede their ability to provide adequate support and guidance. American Indian parents may also be affected by intergenerational transmission of trauma and loss of traditional parenting practices, as a result of forced boarding school and/or relocation. Members of a community-university partnership sought to interrupt cycles of violence and poor mental health of youth through a culturally-grounded intervention for youth and their parents that focused on healing historical trauma, strengthening positive parenting practices and social skills, reconnecting to traditional cultural knowledge, and improving parent-child relationships/communication. This article describes parental involvement and its challenges and provides mixed-method results for 10 parents related to enculturation, parenting practices, parent-child communication, family cohesion, historical loss and associated symptoms, and community involvement.


Outcome of pregnancies complicated by oligohydramnios or anhydramnios of renal origin.
To evaluate the outcome of fetuses with oligohydramnios due to kidney anomalies. A retrospective study was performed of all pregnancies diagnosed with oligohydramnios and associated kidney anomalies during the period 2000-2008. Outcome included pregnancy outcome, mortality, and morbidity. Morbidity included renal function based on the glomerular filtration rate (GFR) during follow-up. A total of 71 pregnancies were evaluated; 36 fetuses presented on ultrasound with cystic dysplasia, 15 with polycystic kidney disease (PKD) and 20 with hydronephrosis. Twenty-three (32%) had associated anomalies. In 49 fetuses (69%), the diagnosis had been made before 24 weeks of gestational age (GA); 41 of those pregnancies were terminated. Twenty-five neonates were live born: 10 survived, 15 died. Prognostic factors for survival included GA at diagnosis (32.2 weeks for survivors vs 28.1 weeks for non-survivors; P = 0.02), diagnosis of hydronephrosis (7 in the survivors vs 4 in the non-survivors: P = 0.05), isolated anomaly (9 in the survivors vs 7 in the non-survivors: P = 0.04). Severity of oligohydramnios (1 case of anhydramnios in the survivors vs 7 in the non-survivors: P = 0.08) was not significant. The 1-year GFR was below 50 mL/min.1.73 m(2) in four of the ten survivors. The prognosis of early onset renal oligohydramnios is poor. Predictive determinants of survival are: GA at diagnosis, nature of renal anomaly (hydronephrosis vs other), and presence of associated anomalies.


Sympathetic ophthalmia presenting with signs of frosted branch angiitis: Report of a case.
Sympathetic ophthalmia is an ocular inflammatory disease commonly associated with penetrating trauma. We report a case of sympathetic ophthalmia who had Dalen-Fuchs nodules on presentation and developed a frosted branch angiitis (FBA)-like picture which is not a known feature of this disease. A 25-year-old male patient was seen 8 months following penetrating trauma to the left eye. He was treated with oral steroids and immunosuppressives. Fundus fluorescein angiography confirmed the presence of perivascular retinitis; optical coherence tomography showed retinal thickening and ultrasonography showed peripapillary choroidal thickening. Atypical features such as FBA in cases of sympathetic ophthalmia can be present and can indicate an ongoing active inflammation. Early aggressive management is required to prevent visual morbidity.


[Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration].
Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.


Acquired factor VIII deficiency presenting as a floor of the mouth swelling.
The authors report the case of a patient with previously undiagnosed acquired haemophilia A who presented to the accident and emergency department with a swollen tongue and difficulty in swallowing. There were no signs of trauma or obvious dental infection. She was admitted onto a high dependency unit for observation. Over the course of the day, the floor of her mouth and neck became increasingly swollen to the extent that she developed breathing difficulties. She was transferred to an intensive care unit, where she was intubated to protect her airway from further compromise. Acquired factor VIII deficiency was diagnosed and appropriate treatment commenced. Despite intervention, her respiratory and cardiovascular functions deteriorated. Following discussions between the medical specialities involved in her care and her family, the decision was made to withdraw support. The patient passed away 96 h after admission.


Psychological stress and coping: framework for poststroke psychosocial care.
The ability to deal with and manage a chronic condition such as stroke requires a learning process embedded in personal experience that is often emotionally taxing as well as physically fatiguing. Stroke survivors typically need help in balancing demands and resources and in preventing or effectively coping with stress emotions to conserve energy. The major constructs outlined in this article provide a framework for psychosocial care to promote the experience of wellness in stroke survivors.


Measurement Properties of Isokinetic Dynamometry for Assessment of Shoulder Muscle Strength: A Systematic Review.
To investigate the evidence of measurement properties of isokinetic dynamometry (ID) for assessment of shoulder muscle strength in healthy individuals and patients with nonneurologic shoulder pathology. Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Physiotherapy Evidence Database were searched up to February 2020 without restrictions. Reference lists and citations were hand-searched. Two review authors independently included studies that met the following criteria: (1) evaluated measurement properties of ID when used on the glenohumeral joint and (2) included individuals 18 years and older. Studies including patients with neurologic, neuromuscular, or systemic diseases or critical illness were excluded. The quality assessment and data synthesis were performed according to the COnsensus-based Standards for the selection of health Measurement INstruments methodology. Twenty-one studies with a total of 597 participants were included. The results were combined separately for isometric, concentric, and eccentric test mode; for the velocities 30°/s-60°/s, 90°/s, 120°/s, and 240°/s; for the seated, supine, and standing position; and for internal rotation (IR), external rotation (ER), and the ER/IR ratio. The reliability of ID was overall sufficient with the majority of intraclass correlation coefficients ≥0.70. The quality of evidence was moderate or low for 20 of 30 strata examined. The measurement error results were rated as insufficient for all strata. The SEM ranged from 4%-28%. The quality of evidence varied depending of strata examined. The reliability of ID for measurement of shoulder strength was overall sufficient for all positions, velocities, and modes of strength. The measurement error was not sufficient. Because most studies used the seated position, the velocities 30°/s-60°/s or 120°/s, and the concentric test mode, the quality of evidence was highest for these conditions.


Compositional Changes in Hydroponically Cultivated Salicornia europaea at Different Growth Stages.
Abiotic stress conditions, such as salinity, affect plant development and productivity and threaten the sustainability of agricultural production. Salt has been proven to accumulate in soil and water over time as a result of various anthropogenic activities and climatic changes. Species of the genus Salicornia thrive in the most saline environments and have a wide climatic tolerance. They can be found in a variety of subtropical, oceanic, and continental environments. This study aims to establish Salicornia europaea as a novel source of plant-based compounds that can grow in areas unsuitable for other crops. The morphological and compositional changes in the tissues of S. europaea in different consecutive developmental stages have not been investigated so far. Therefore, a comprehensive study of changes during the lifecycle of S. europaea was carried out, following changes in the plant's composition, including biomass yield, and soluble and insoluble compounds. For this, plants were cultivated in hydroponics for 15 weeks and harvested weekly to analyze biomass production, to determine soluble and insoluble compounds, protein content, and polyphenols. According to the results, glucan, xylan, and lignin increase with plant age, while water extractives decrease. Protein content is higher in young plants, while flavonoid content depends on the phenological stage, decreasing in the early flowering stage and then increasing as plants enter early senescence. Our results can aid in finding the optimal harvesting stage of S. europaea, depending on the component of interest.


A general strategy for cellular reprogramming: the importance of transcription factor cross-repression.
Transcription factor cross-repression is an important concept in cellular differentiation. A bistable toggle switch constitutes a molecular mechanism that determines cellular commitment and provides stability to transcriptional programs of binary cell fate choices. Experiments support that perturbations of these toggle switches can interconvert these binary cell fate choices, suggesting potential reprogramming strategies. However, more complex types of cellular transitions could involve perturbations of combinations of different types of multistable motifs. Here, we introduce a method that generalizes the concept of transcription factor cross-repression to systematically predict sets of genes, whose perturbations induce cellular transitions between any given pair of cell types. Furthermore, to our knowledge, this is the first method that systematically makes these predictions without prior knowledge of potential candidate genes and pathways involved, providing guidance on systems where little is known. Given the increasing interest of cellular reprogramming in medicine and basic research, our method represents a useful computational methodology to assist researchers in the field in designing experimental strategies.


Patient use of the Internet to obtain health information.
With increasing use of the internet by patients, questions are being raised in the press and by professionals on whether members of the public may be harming themselves by gaining access to previously hidden material. A search of the literature from a variety of sources revealed that the evidence was conflicting. Because the internet is here to stay, it is suggested that health professionals use it in partnership with patients, at the same time acknowledging its pitfalls.


Complete videothoracoscopic en-bloc resection of lung cancer invading the diaphragm.
Locally advanced non-small cell lung cancer invading the diaphragm is an infrequent clinical presentation. A 74-year-old male patient was operated using video-assisted thoracoscopic surgery in our clinic for a tumor originating from the right lower lobe. A right lower lobectomy with diaphragmatic resection was performed to the tumor with a diameter of 3 cm that invaded the diaphragm, and the resulting defect was repaired primarily with video-assisted thoracoscopic surgery. The patient did not develop complications in the postoperative period and was discharged on Day 6. In conclusion, patients with non-small cell lung cancer invasive to the diaphragm can be even safely operated with the video-assisted thoracoscopic surgery.


Shift models for dose-finding in partially ordered groups.
Limited options are available for dose-finding clinical trials requiring group-specific dose selection. While conducting parallel trials for groups is an accessible approach to group-specific dose selection, this approach allows for maximum tolerated dose selection that does not align with clinically meaningful group order information. The two-stage continual reassessment method is developed for dose-finding in studies involving three or more groups where group frailty order is known between some but not all groups, creating a partial order. This is an extension of the existing continual reassessment method shift model for two ordered groups. This method allows for dose selection by group, where maximum tolerated dose selection follows the known frailty order among groups. For example, if a group is known to be the most frail, the recommended maximum tolerated dose for this group should not exceed the maximum tolerated dose recommended for any other group. With limited alternatives for dose-finding in partially ordered groups, this method is compared to two alternatives: (1) an existing method for dose-finding in partially ordered groups which is less computationally accessible and (2) independent trials for each group using the two-stage continual reassessment method. Simulation studies show that when ignoring information on group frailty, using independent continual reassessment method trials by group, 30% of simulations would result in maximum tolerated dose selection that is out of order between groups. In addition, the two-stage continual reassessment method for partially ordered groups selects the maximum tolerated dose more often and assigns more patients to the maximum tolerated dose compared to using independent continual reassessment method trials within each group. Simulation results for the proposed method and the less computationally accessible approach are similar. The proposed continual reassessment method for partially ordered groups ensures appropriate maximum tolerated dose order and improves accuracy of maximum tolerated dose selection, while allowing for trial implementation that is computationally accessible.


Molecular docking analysis of furfural and isoginkgetin with heme oxygenase I and PPARγ.
It is of interest to document the molecular docking analysis based binding data of furfural and isoginkgetin with heme oxygenase I and PPARγ in the context of inflammation for further consideration in drug design and development.


Optically Imaged Striped Domains of Nonequilibrium Electronic and Nuclear Spins in a Fractional Quantum Hall Liquid.
Using photoluminescence microscopy enhanced by magnetic resonance, we visualize in real space both electron and nuclear polarization occurring in nonequilibrium fraction quantum Hall (FQH) liquids. We observe stripelike domain regions comprising FQH excited states which discretely form when the FQH liquid is excited by a source-drain current. These regions are deformable and give rise to bidirectionally polarized nuclear spins as spin-resolved electrons flow across their boundaries.


CD326 (EpCAM) testing by flow cytometric BerEP4 antibody is a useful and rapid adjunct to histopathology.
Flow cytometry has been traditionally used to diagnose leukaemia and lymphoma in peripheral blood, bone marrow, body fluids, and tissue samples. The diagnosis of a malignant epithelial tumour is usually made by correlation between histopathologic appearance and the use of immunohistochemical staining. A CE approved BerEP4 antibody (anti-EpCAM, CD326) is available for flow cytometric testing, but has been evaluated predominantly in body fluids in the current literature. In this study, we have evaluated the performance of this antibody in detecting the presence of epithelial cells in tissue samples which have traditionally been reported as CD45 negative cells by flow cytometry. Among the 42 cases studied, 21 (50%) were found to be positive for CD326, thereby suggesting epithelial differentiation. The results had good concordance rates (97.6%) with final histopathological diagnosis. The results clearly show that flow cytometric testing for BerEP4 (CD326) can be a useful method for diagnosing nonhaematological malignancies that are poorly differentiated. As this is a rapid method for identifying epithelial differentiation, it can help the histopathologists tailor and rationalise the immunohistochemical panel, with the potential benefits of improving reporting times and work-flow in the laboratory. © 2017 International Clinical Cytometry Society.


Spondylothoracic dysplasia. A report of ten cases with follow-up.
Details of ten new cases of spondylothoracic dysplasia (the Jarcho-Levin syndrome) are presented. During follow-up, lasting between 8 and 21 years, two children in this group died. Our observations did not confirm Heilbronner's theory concerning the existence of two distinctive types of this syndrome: Type 1 or fatal, and Type 2, with a normal longevity. From the two illustrative cases presented in some detail, and the pertinent literature review, familiarity with spondylothoracic dysplasia is necessary in order to avoid an unjustifiably pessimistic prognosis and to permit correct parent counseling.


RNA-Seq Analysis to Detect Abnormal Fusion Transcripts Linked to Chromothripsis.
RNA-Seq approach enables the detection and characterization of fusion or chimeric transcript associated to complex genome rearrangement. Until now, these events are classically identified at DNA level.Here we describe a complete procedure including a novel way of analyzing reads that combines genomic locations and local coverage to directly infer chimeric junctions with a high sensitivity and specificity, allowing identification of different classes of chimeric RNA events. We also recommend the best practices for the bioinformatics analysis and describe the experimental process for RNA validation using real-time PCR and sequencing.


Subjective cognitive complaints and subjective cognition following electroconvulsive therapy for depression: A systematic review and meta-analysis.
Subjective cognitive complaints represent a leading reason for suboptimal prescription of electroconvulsive therapy, the most acutely effective treatment for depression. However, research findings regarding their presentation are conflicting. To describe, quantify and explain the variability in subjective cognitive complaints and subjective cognition following electroconvulsive therapy for depression. We searched systematically PubMed, Embase, PsycARTICLES, CINAHL and relevant reviews for research published from 1 January 1972 to 31 August 2020. We included all independent studies of patients whose subjective cognition was assessed following brief-pulse electroconvulsive therapy for depression. Three meta-analyses were conducted to quantify: (1) the prevalence of patients presenting with cognitive complaints following electroconvulsive therapy; (2) the pre-post electroconvulsive therapy change in subjective cognition and (3) the association between change in depressive symptoms and change in cognitive complaints. Effect sizes were calculated using random-effects models. Eight prespecified demographic and clinical moderators of between-study variability were assessed using sub-group analyses and meta-regressions. Data from 72 studies including 5699 participants were meta-analysed. Weighted mean prevalence of patients with cognitive complaints was 48.1% (95% confidence interval = [42.3%, 53.9%]). The type of subjective measure used significantly impacted the pre-post electroconvulsive therapy change in subjective cognition, showing, respectively, large improvement (g = 0.81; 95% confidence interval = [0.59, 1.03]) after electroconvulsive therapy with the Squire Self-Rating Scale of Memory and small worsening (g = -0.48; 95% confidence interval = [-0.70, -0.26]) with 1-item memory scales. The strongest predictors of improved post-electroconvulsive therapy subjective cognition were increased age and larger post-electroconvulsive therapy decrease in depressive symptoms. The weighted mean correlation between pre-post electroconvulsive therapy decrease in depressive symptoms and pre-post electroconvulsive therapy decrease in cognitive complaints was 0.46 (95% confidence interval = [0.39, 0.53]). Variability in subjective cognition following electroconvulsive therapy is mostly explained by the degree of post-treatment persisting depression and by the subjective assessment used. Scales measuring exclusively subjective worsening present limited clinical utility and instruments allowing the detection of both improvement and worsening in subjective cognition should be preferred.


Repetitive Transcranial Magnetic Stimulation Improves Mild Cognitive Impairment Associated with Alzheimer's Disease in Mice by Modulating the miR-567/NEUROD2/PSD95 Axis.
Mild cognitive impairment (MCI) is a typical symptom of early Alzheimer's disease (AD) and is driven by the dysfunction of microRNAs (miRs). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique for handling neuropsychiatric disorders and has universally effects on the functions of miRs. In the current study, the improvement effects of rTMS on MCI associated with AD were explored by focusing on miR-567/NEUROD2/PSD95 axis. MCI was induced in mice using scopolamine and was treated with rTMS of two frequencies (1 Hz and 10 Hz). The changes in cognitive function, brain structure, neurotrophic factor levels, and activity of miR-567/NEUROD2/PSD95 axis were assessed. The interaction between rTMS and miR-567 was further verified by inducing the level of miR-567 in AD mice. The administrations of rTMS improved the cognitive function of AD mice and attenuated brain tissue destruction, which were associated with the restored production of BDNF and NGF. Additionally, rTMS administrations suppressed the expression of miR-567 and up-regulated the expressions of NEUROD2 and PSD95, which contributed to the improved condition in central nerve system. With the induced level of miR-567, the effects of rTMS were counteracted: the learning and memorizing abilities of mice were impaired, the brain neuron viability was suppressed, and the production of neurotrophic factors was suppressed even under the administration of rTMS. The changes in brain function and tissues were associated with the inhibited expressions of NEUROD2 and PSD95. The findings outlined in the current study demonstrated that rTMS treatment could protect brain against AD-induced MCI without significant side effects, and the function depended on the inhibition of miR-567.


Chest CT of Lung Injury 1 Year after COVID-19 Pneumonia: The CovILD Study.
Background The long-term pulmonary sequelae of COVID-19 is not well known. Purpose To characterize patterns and rates of improvement of chest CT abnormalities 1 year after COVID-19 pneumonia. Materials and Methods This was a secondary analysis of a prospective, multicenter observational cohort study conducted from April 29 to August 12, 2020, to assess pulmonary abnormalities at chest CT approximately 2, 3, and 6 months and 1 year after onset of COVID-19 symptoms. Pulmonary findings were graded for each lung lobe using a qualitative CT severity score (CTSS) ranging from 0 (normal) to 25 (all lobes involved). The association of demographic and clinical factors with CT abnormalities after 1 year was assessed with logistic regression. The rate of change of the CTSS at follow-up CT was investigated by using the Friedmann test. Results Of 142 enrolled participants, 91 underwent a 1-year follow-up CT examination and were included in the analysis (mean age, 59 years ± 13 [SD]; 35 women [38%]). In 49 of 91 (54%) participants, CT abnormalities were observed: 31 of 91 (34%) participants showed subtle subpleural reticulation, ground-glass opacities, or both, and 18 of 91 (20%) participants had extensive ground-glass opacities, reticulations, bronchial dilation, microcystic changes, or a combination thereof. At multivariable analysis, age of more than 60 years (odds ratio [OR], 5.8; 95% CI: 1.7, 24; P = .009), critical COVID-19 severity (OR, 29; 95% CI: 4.8, 280; P < .001), and male sex (OR, 8.9; 95% CI: 2.6, 36; P < .001) were associated with persistent CT abnormalities at 1-year follow-up. Reduction of CTSS was observed in participants at subsequent follow-up CT (P < .001); during the study period, 49% (69 of 142) of participants had complete resolution of CT abnormalities. Thirty-one of 49 (63%) participants with CT abnormalities showed no further improvement after 6 months. Conclusion Long-term CT abnormalities were common 1 year after COVID-19 pneumonia. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leung in this issue.


Use of dynamic telepathology in Mohs surgery: a feasibility study.
Telepathology is an emerging technology for remote pathology consultation and diagnosis. To assess the diagnostic accuracy and utility of a dynamic telepathology system in the setting of Mohs surgery. Using a dynamic telepathology system, a single dermatopathologist at a remote site assessed the following cases: (1) 50 fixed-tissue slides of basal and squamous cell carcinomas for pathologic diagnosis; (2) 40 frozen-section slides from Mohs surgery for the presence or absence of tumor; (3) 20 frozen-section slides from Mohs surgery for intraoperative consultation with the Mohs surgeon. All 110 slides were then randomly reviewed by the same dermatopathologist by conventional light microscopy. Telepathology and conventional light microscopy diagnoses were then compared. There was complete agreement between telepathology and conventional light microscopy diagnoses. Dynamic telepathology is a convenient, useful, and accurate system for remote diagnosis and consultation in the setting of Mohs surgery.


Sex and nitric oxide bioavailability interact to modulate interstitial Po2 in healthy rat skeletal muscle.
Premenopausal women express reduced blood pressure and risk of cardiovascular disease relative to age-matched men. This purportedly relates to elevated estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated vasorelaxation. We tested the hypotheses that female rat skeletal muscle would: 1) evince a higher O2 delivery-to-utilization ratio (Q̇o2/V̇o2) during contractions; and 2) express greater modulation of Q̇o2/V̇o2 with changes to NO bioavailability compared with male rats. The spinotrapezius muscle of Sprague-Dawley rats (females = 8, males = 8) was surgically exposed and electrically-stimulated (180 s, 1 Hz, 6 V). OxyphorG4 was injected into the muscle and phosphorescence quenching employed to determine the temporal profile of interstitial Po2 (Po2is, determined by Q̇o2/V̇o2). This was performed under three conditions: control (CON), 300 µM sodium nitroprusside (SNP; NO donor), and 1.5 mM Nω-nitro-l-arginine methyl ester (l-NAME; NOS blockade) superfusion. No sex differences were found for the Po2is kinetics parameters in CON or l-NAME ( P > 0.05), but females elicited a lower baseline following SNP (males 42 ± 3 vs. females 36 ± 2 mmHg, P < 0.05). Females had a lower ΔPo2is during contractions following SNP (males 22 ± 3 vs. females 17 ± 2 mmHg, P < 0.05), but there were no sex differences for the temporal response to contractions ( P > 0.05). The total NO effect (SNP minus l-NAME) on Po2is was not different between sexes. However, the spread across both conditions was shifted to a lower absolute range for females (reduced SNP baseline and greater reduction following l-NAME). These data support that females have a greater reliance on basal NO bioavailability and males have a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO. NEW & NOTEWORTHY Interstitial Po2 (Po2is; determined by O2 delivery-to-utilization matching) plays an important role for O2 flux into skeletal muscle. We show that both sexes regulate Po2is at similar levels at rest and during skeletal muscle contractions. However, modulating NO bioavailability exposes sex differences in this regulation with females potentially having a greater reliance on basal NO bioavailability and males having a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.


C1q/Tumor Necrosis Factor-Related Protein 9: Basics and Therapeutic Potentials.
C1q/tumor necrosis factor-related protein 9 (CTRP9) is a newly discovered adipokine that is the closest paralog of adiponectin. Proteolytic cleavage of CTRP9 leads to the release of the globular domain (gCTRP9), which serves as the major circulating subtype. After binding with adiponectin receptor 1 (AdipoR1) and N-cadherin, CTRP9 activates various signaling pathways to regulate glucose and lipid metabolism, vasodilation and cell differentiation. Throughout human development and adult life, CTRP9 controls many biological phenomena. simultaneously, abnormal gene or protein expression of CTRP9 is accompanied by a wide range of human pathological phenomena. In this review, we briefly introduce CTRP9 and its associated signaling pathways and physiological functions, which may be helpful in the understanding of the occurrence of diseases. Moreover, we summarize the broader research prospects of CTRP9 and advances in therapeutic intervention. In recent years, CTRP9 has attracted extensive attention due to its role in the pathogenesis of various diseases, providing further avenues for its exploitation as a potential biomarker or therapeutic target.


Spatial patterns of cadmium and lead deposition on and adjacent to National Park Service lands in the vicinity of Red Dog Mine, Alaska.
Heavy metal escapement associated with ore trucks is known to occur along the DeLong Mountain Regional Transportation System (DMTS) haul road corridor in Cape Krusenstern National Monument, northwest Alaska. Heavy metal concentrations in Hylocomium splendens moss (n = 226) were used in geostatistical models to predict the extent and pattern of atmospheric deposition of Cd and Pb on Monument lands. A stratified grid-based sample design was used with more intensive sampling near mine-related activity areas. Spatial predictions were used to produce maps of concentration patterns, and to estimate the total area in 10 moss concentration categories. Heavy metal levels in moss were highest immediately adjacent to the DMTS haul road (Cd > 24 mg/kg dw; Pb > 900 mg/kg dw). Spatial regression analyses indicated that heavy metal deposition decreased with the log of distance from the DMTS haul road and the DMTS port site. Analysis of subsurface soil suggested that observed patterns of heavy metal deposition reflected in moss were not attributable to subsurface lithology at the sample points. Further, moss Pb concentrations throughout the northern half of the study area were high relative to concentrations previously reported from other Arctic Alaska sites. Collectively, these findings indicate the presence of mine-related heavy metal deposition throughout the northern portion of Cape Krusenstern National Monument. Geospatial analyses suggest that the Pb depositional area extends 25 km north of the haul road to the Kisimilot/Iyikrok hills, and possibly beyond. More study is needed to determine whether higher moss heavy metal concentrations in the northernmost portion of the study area reflect deposition from mining-related activities, weathering from mineralized Pb/Zn outcrops in the broader region, or a combination of the two. South of the DMTS haul road, airborne deposition appears to be constrained by the Tahinichok Mountains. Heavy metal levels continue to diminish south of the mountains, reaching a minimum in the southernmost portion of the study area near the Igichuk Hills (45 km from the haul road). The influence of the mine site was not studied.


Histaminergic regulation of food intake.
Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei. The activation of different histamine receptors is associated with differential effects on neuronal activity, mediated by their different G protein-coupling. Consequently, activation of H1R has opposing effects on food intake to that of H3R: H1R activation suppresses food intake, while H3R activation mediates an orexigenic response. The central histaminergic system has been implicated in atypical antipsychotic-induced weight gain and has been proposed as a potential therapeutic target for the treatment of obesity. It has also been demonstrated to interact with other major regulators of energy homeostasis, including the central melanocortin system and the adipose-derived hormone leptin. However, the exact mechanisms by which the histaminergic system contributes to the modification of these satiety signals remain underexplored. The present review focuses on recent advances in our understanding of the central histaminergic system's role in regulating feeding and highlights unanswered questions remaining in our knowledge of the functionality of this system.


Chondrocyte-mediated breakdown of cartilage.
Chondrocyte-mediated degradation of cartilage was studied using bovine nasal cartilage discs cultured for up to 8 days in the presence or absence of chemically defined agents. Breakdown, assessed quantitatively as proteoglycan released into culture medium and qualitatively by gel filtration of (medium and cartilage) products, was potently stimulated by highly purified interleukin-1 (IL-1), bacterial lipopolysaccharides, and prostaglandin F2 alpha. IL-1 action was abolished by anti-IL-1 antibodies but unaffected by hydrocortisone. LPS-stimulated breakdown was reversibly inhibited by glucocorticoid hormones, indomethacin, and cAMP. In addition to their usefulness in probing chondrocyte degradative pathways, several of these agents may be of pathogenetic and clinical significance.


Protein-protein docking with multiple residue conformations and residue substitutions.
The protein docking problem has two major aspects: sampling conformations and orientations, and scoring them for fit. To investigate the extent to which the protein docking problem may be attributed to the sampling of ligand side-chain conformations, multiple conformations of multiple residues were calculated for the uncomplexed (unbound) structures of protein ligands. These ligand conformations were docked into both the complexed (bound) and unbound conformations of the cognate receptors, and their energies were evaluated using an atomistic potential function. The following questions were considered: (1) does the ensemble of precalculated ligand conformations contain a structure similar to the bound form of the ligand? (2) Can the large number of conformations that are calculated be efficiently docked into the receptors? (3) Can near-native complexes be distinguished from non-native complexes? Results from seven test systems suggest that the precalculated ensembles do include side-chain conformations similar to those adopted in the experimental complexes. By assuming additivity among the side chains, the ensemble can be docked in less than 12 h on a desktop computer. These multiconformer dockings produce near-native complexes and also non-native complexes. When docked against the bound conformations of the receptors, the near-native complexes of the unbound ligand were always distinguishable from the non-native complexes. When docked against the unbound conformations of the receptors, the near-native dockings could usually, but not always, be distinguished from the non-native complexes. In every case, docking the unbound ligands with flexible side chains led to better energies and a better distinction between near-native and non-native fits. An extension of this algorithm allowed for docking multiple residue substitutions (mutants) in addition to multiple conformations. The rankings of the docked mutant proteins correlated with experimental binding affinities. These results suggest that sampling multiple residue conformations and residue substitutions of the unbound ligand contributes to, but does not fully provide, a solution to the protein docking problem. Conformational sampling allows a classical atomistic scoring function to be used; such a function may contribute to better selectivity between near-native and non-native complexes. Allowing for receptor flexibility may further extend these results.


Gland New Psychosis: New Onset Adult Psychosis with Suicidal Ideation and Attempt in the Setting of Thyroid Storm.
We present a case of new onset psychosis in the setting of thyroid storm in a woman with no previous psychiatric history. The patient presented with ongoing suicidal ideation, a suicide attempt that was interrupted by her husband, and audio and visual hallucinations. The patient was placed on a psychiatric hold and treated for thyrotoxicosis as well as psychosis. Treatment of the thyroid hormone overload resulted in a rapid resolution of her symptoms; she was discharged in excellent condition, and she has had no repeat hallucinations or self-injury ideation or attempts since. Although rare, thyrotoxicosis is a potentially life-threatening cause of psychiatric illness and should always be kept on the differential diagnosis for a patient with a first episode of psychosis. This case highlights how thyroid storm physiology, beyond its well-studied hemodynamic and metabolic instability, can be potentially fatal due to psychiatric sequelae. It also highlights the crucial role of a thorough history and physical exam in all patients.


Iodine content of salt in Lae city of Papua New Guinea.
Papua New Guinea (PNG) is among those areas of the world where soils lack iodine. Iodine deficiency leads to a number of disorders including goitre and cretinism. The PNG government has chosen to promote the consumption of adequately iodised salt as one of its intervention programmes to eradicate the iodine deficiency disorders. A study was undertaken to assess the iodine content of salt in the distribution chain in Lae, as well as to assess the per capita salt consumption in the city. It was found that the average salt consumption was 6.59 g/d. However, not all the Lae population were consuming adequately iodised salt. Only 48% of salt samples from one school were adequately iodised. The percentage of wholesale salt samples containing more than the standard 30 p.p.m. iodine increased from 61.5% in 1996 to 90.9% in 1997. The iodine content of the retail samples were 73.5% and 87.1% in 1996 and 1997, respectively. Stricter, sustained and systematic monitoring of the quality of iodised salt procured and distributed in Lae is called for to ensure consumption of adequately iodised salt.


Biosynthesis of butyric acid by Clostridium tyrobutyricum.
Butyric acid (C3H7COOH) is an important chemical that is widely used in foodstuffs along with in the chemical and pharmaceutical industries. The bioproduction of butyric acid through large-scale fermentation has the potential to be more economical and efficient than petrochemical synthesis. In this paper, the metabolic pathways involved in the production of butyric acid from Clostridium tyrobutyricum using hexose and pentose as substrates are investigated, and approaches to enhance butyric acid production through genetic modification are discussed. Finally, bioreactor modifications (including fibrous bed bioreactor, inner disk-shaped matrix bioreactor, fibrous matrix packed in porous levitated sphere carriers), low-cost feedstocks, and special treatments (including continuous fermentation with cell recycling, extractive fermentation with solvent, using different artificial electron carriers) intended to improve the feasibility of commercial butyric acid bioproduction are summarized.


Diffusion in a two-dimensional energy landscape in the presence of dynamical correlations and validity of random walk model.
Diffusion in a multidimensional energy surface with minima and barriers is a problem of importance in statistical mechanics and it also has wide applications, such as protein folding. To understand it in such a system, we carry out theory and simulations of a tagged particle moving on a two-dimensional periodic potential energy surface, both in the presence and absence of noise. Langevin dynamics simulations at multiple temperatures are carried out to obtain the diffusion coefficient of a solute particle. Friction is varied from zero to large values. Diffusive motion emerges in the limit of a long time, even in the absence of noise. Noise destroys the correlations and increases diffusion at small friction. Diffusion thus exhibits a nonmonotonic friction dependence at the intermediate value of the damping, ultimately converging to our theoretically predicted value. The latter is obtained using the well-established relationship between diffusion and random walk. An excellent agreement is obtained between theory and simulations in the high-friction limit but not so in the intermediate regime. We explain the deviation in the low- to intermediate-friction regime using the modified random walk theory. The rate of escape from one cell to another is obtained from the multidimensional rate theory of Langer. We find that enhanced dimensionality plays an important role. To quantify the effects of noise on the potential-imposed coherence on the trajectories, we calculate the Lyapunov exponent. At small friction values, the Lyapunov exponent mimics the friction dependence of the rate.


Titratable macroions in multivalent electrolyte solutions: Strong coupling dressed ion approach.
We present a theoretical description of the effect of polyvalent ions on the interaction between titratable macroions. The model system consists of two point-like macroions with dissociable sites, immersed in an asymmetric ionic mixture of monovalent and polyvalent salts. We formulate a dressed ion strong coupling theory, based on the decomposition of the asymmetric ionic mixture into a weakly electrostatically coupled monovalent salt and into polyvalent ions that are strongly electrostatically coupled to the titratable macro-ions. The charge of the macroions is not considered as fixed, but is allowed to respond to local bathing solution parameters (electrostatic potential, pH of the solution, and salt concentration) through a simple charge regulation model. The approach presented, yielding an effective polyvalent-ion mediated interaction between charge-regulated macroions at various solution conditions, describes the strong coupling equivalent of the Kirkwood-Schumaker interaction.


Controversies in contraception for women with epilepsy.
Contraception is an important choice that offers autonomy to women with regard to prevention of unintended pregnancies. There is wide variation in the contraceptive practices between continents, countries, and societies. The medical eligibility for contraception for sexually active women with epilepsy (WWE) is determined by the type of anti-epileptic drugs (AEDs) that they use. Enzyme inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine increase the metabolism of orally administered estrogen (and progesterone to a lesser extent). Estrogen can increase the metabolism of certain AEDs, such as lamotrigine, leading to cyclical variation in its blood level with resultant adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase the risk of osteoporosis and fracture in WWE. The potential interactions between AEDs and hormonal contraception need to be discussed with all women in reproductive age-group. The alternate options of oral contraception such as intrauterine copper device, intrauterine levonorgestrel release system, and supplementary protection with barriers need to be presented to them. World Health Organization has recommended to avoid combination contraceptive pills containing estrogen and progesteron in women who desire contraception and in breastfeeding mothers. Care providers need to consider the option of non-enzyme-inducing AEDs while initiating long-term treatment in adolescent and young WWE.


Effects of intravenous cibenzoline on ventricular vulnerability and electrophysiology in patients with sustained ventricular tachycardia in comparison to a control group.
The electrophysiologic effects of intravenous (i.v. 1.5 mg/kg) cibenzoline were investigated in 13 patients with organic heart disease and supraventricular arrhythmias (control group) and 13 patients with drug refractory sustained ventricular tachycardia (VT group). In both groups, cibenzoline increased the effective refractory period (ERP) of the right ventricle (p less than or equal to 0.05), QRS duration (p less than or equal to 0.01), and QTc duration (p less than or equal to 0.01). Cycle length of the VT was increased from 311 +/- 73 to 393 +/- 119 ms (p less than or equal to 0.05) as well. The increase in QTc duration was more pronounced (p less than or equal to 0.05) in the VT group as compared with the control group. In four patients in the VT group with the largest increase in QRS-, QTc duration and cycle length of the VT proarrhythmia was noted after i.v. cibenzoline. Cibenzoline plasma levels were not significantly different between the two study groups. In the VT group, induction of VT was prevented in 2 patients, more difficult in 2 patients, easier in 1 patient, and unchanged in 5 patients. Spontaneous occurrence of the VT or induction by atrial stimulation was noted in 4 patients. In the control group, ventricular vulnerability remained unchanged. Cibenzoline may be effective in selected patients with drug refractory VT. In such patients, the increase in QTc duration was more pronounced as compared with a control group.


Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.
The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of "hot spots" with/without central photopenia and "cold spots" detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more "hot spots" with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more "cold spots" than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.


Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin.
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained. Serine uptake and glycine secretion are elevated suggesting increased requirement for one-carbon contribution. Consistently, vulnerability to serine depletion increases. The decrease in glycolysis is coupled to elevated oxidative phosphorylation, which is diminished by metformin, further increasing cell death and inhibiting tumor growth. Neither HK2 silencing nor metformin alone inhibits mTORC1, but their combination inhibits mTORC1 in an AMPK-independent and REDD1-dependent mechanism. Finally, HK2 silencing synergizes with sorafenib to inhibit tumor growth.


The health status of children without resident permit consulting the Children's Hospital of Lausanne.
To assess social, economic and medical data concerning children without a resident permit taken into care by the Children's Hospital of Lausanne (HEL) in order to evaluate their specific needs. Prospective exploratory study by a questionnaire including the socio-demographic, medical and education data of 103 children without a resident permit, who consulted the HEL for the first time between August 2003 and March 2006. These children were then recalled for a second check-up one year later in order to allow a regular monitoring. Eighty-seven percent of the children were native of Latin America, 36% being less than two years old. This population of children lived in precarious conditions with a family income lower than the poverty level (89% of the families with less than 3100 CHF/month). Forty-five percent of the children had a health insurance. The main reasons for consultation were infectious diseases, a check-up requested by the school or a check-up concerning newborn children. Most of them were in good health and the others were affected by illnesses similar to those found in other children of the same age. At least 13% of the children were obese and 27% were overweight. All children who were of educational age went to school during the year after the first check-up and 48% were affiliated to a health insurance. The majority of the children from Latin America lived in very precarious conditions. Their general health status was good and most of them could benefit from regular check-ups. Prevention, focused on a healthier life style, was particularly important among this population characterised by a high incidence of overweight and obesity.


Substance P elicited grooming in the mouse: behavioral and pharmacological characteristics.
Substance P undercapeptide produces intense grooming after central injection. To characterize further this syndrome at behavioral and psychopharmacological level: (a) substance P elicited grooming was compared to spontaneously occurring grooming for their respective behavioral characteristics, and (b) a variety of centrally active substances were injected in an attempt to modify the normal occurrence of the grooming syndrome. Manipulations of opioid systems did not affect grooming, nor did a variety of other peptides. However, central injections of neurotensin significantly inhibited grooming. This interaction may represent a functional behavioral correlate of the established neuroanatomical interactions of the above substances.


A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats.
Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT), a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.


Comparison of high-flow nasal oxygen therapy with conventional oxygen therapy and noninvasive ventilation in adult patients with acute hypoxemic respiratory failure: A meta-analysis and systematic review.
The role of high-flow nasal oxygen (HFNO) therapy in adult patients with acute hypoxemic respiratory failure is controversial. This meta-analysis of prospective randomized controlled trials (RCTs) has been designed to compare HFNO with noninvasive ventilation (NIV) and conventional oxygen therapy in such patients. Initial database searching revealed 336 RCTs, of which 7 were included in this meta-analysis. Five RCTs compared HFNO with standard oxygen therapy, one compared HFNO with NIV, and one compared all three. HFNO did not decrease the requirement of higher respiratory support compared with control group. HFNO was associated with improved respiratory rate and dyspnea score, and better comfort in 3 RCTs, whereas other studies did not find any difference. High-flow nasal oxygen does not offer any benefit over NIV or conventional oxygen therapy in terms of requirement of higher respiratory support.


Muscle oxygenation and EMG activity during isometric exercise in children.
The aim of this study was to examine the time-course of and the relationships between muscle oxygenation, blood volume and myoelectrical manifestations during isometric exercise in children. Twelve healthy children aged 12.5 +/- 1.2 years (mean +/- s) performed an isometric knee extension at 50% of their maximal voluntary contraction (MVC) until exhaustion to assess endurance time (limit time, T(lim)). Changes in muscle oxygenation and blood volume were assessed by near infrared spectroscopy (NIRS). The root mean square (RMS) amplitude and the mean power frequency (MPF) from electromyogram (EMG) signals were obtained, as NIRS parameters, from the vastus lateralis. Mean T(lim) was 117 +/- 34 s. The muscle oxygenation and blood volume curves decreased immediately at the beginning of exercise. Maximal deoxygenation occurred at 50% T(lim), and fell by 76.9% from the resting value. Similarly, minimal blood volume was observed at 50% T(lim); it reached a plateau that lasted until the end of exercise. The kinetics of the MPF and RMS curves were inversely related to time. At the last set of exercises (after 75% T(lim)), a steeper RMS curve and an abrupt decrease in the MPF curve were observed. Significant correlations (r) between muscle oxygenation, blood volume, root mean square amplitude and mean power frequency were observed, which ranged from 0.72 to 0.99. These findings suggest that the fatigue resulting from sustained isometric exercise is related to a decrease in oxygenation and blood volume.


[Neonatal hemolytic anemia after intra-amniotic injection of methylene blue].
The authors report two cases of neonatal hemolytic anemia without methemoglobinemia secondary to intraamniotic injection of 10 mg of methylene blue. Evolution was favourable without exchange transfusion. This emphasizes the importance of searching for a toxic origin in case of neonatal hemolytic anemia without apparent cause.


Role of nuclear factor of activated T cells in chondrogenesis osteogenesis and osteochondroma formation.
Nuclear factor of activated T cells (NFATc) are transcription factors that play a function in the immune response and in osteoclast differentiation. In the present work, we define the function of NFATc2 in chondrogenic and osteogenic cells. Nfatc2loxP/loxP and Nfatc1loxP/loxP;Nfatc2loxP/loxP conditional mice were crossed with Prx1-Cre transgenics to inactivate Nfatc2 singly and with Nfatc1. Femurs and vertebrae were examined by microcomputed tomography (µCT) X-Ray images and histology and analyzed for the presence of osteochondromas. µCT demonstrated that Prx1-Cre;Nfatc2∆/∆ female mice had transient osteopenia and male mice did not have a cancellous or a cortical bone phenotype when compared to control mice. In contrast, the dual inactivation of Nfatc1 and Nfatc2 in Prx1-expressing cells resulted in cancellous osteopenia and small bones at 1 month of age in both sexes. Nfatc1;Nfatc2 deleted mice exhibited a ~ 50% decrease in bone volume and connectivity. Total bone area, periosteal and endocortical bone perimeters and femoral length were reduced indicating smaller bones. As the mice matured, the shortening of the femoral length persisted, but the osteopenic phenotype resolved and cancellous femoral bone of 4-month-old Nfatc1;Nfatc2 deleted mice was not different from controls although male mice had vertebral osteopenia. In addition, Nfatc1;Nfatc2 deleted mice displayed distortion of the distal metaphysis and, as they matured, the articular presence of mineralized tumors with the appearance of osteochondromas. Our studies reveal that NFATc1 and NFATc2 are necessary for optimal bone homeostasis and the suppression of osteochondroma formation.


Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting.
The mechanisms for postoperative nausea and vomiting are numerous and pathways not well elucidated. Although many medications have been developed to help prevent postoperative nausea and vomiting, the search for better approaches to recovery treatment continues. The purpose of this study was to evaluate the effectiveness of isopropyl alcohol (IPA) inhalation for treatment of postoperative nausea and vomiting for patients who have general anesthesia for a surgical procedure. Participants were recruited from an urban hospital on the East Coast of the United States. Participants were assigned to an experimental or control group and IPA inhalation was compared to the standard anti-emetic treatment for rescue treatment in the immediate postoperative period. Postoperative nausea and vomiting was rated using a descriptive ordinal scale. The results of this study show IPA to be effective and that there was no significant difference between the standard treatment protocol and treatment with IPA. Treatment with IPA was significantly more cost effective than standard drug treatment. Further research is recommended to evaluate the length of effectiveness, standard dose needed, most effective mode of inhalation, and factors blocking IPA effectiveness.


[Stereological study on the myocardial protection in mitral valve replacement with beating heart under mild hypothermia].
To appraise objectively the myocardial protective effect of beating heart with mild hypothermia and cardiopulmonary bypass (CPB) with cardiac arrest by cold cardioplegia perfusion during open-heart operation for mitral valve replacement (MVR). Forty patients with rheumatic heart disease were randomly allocated to two groups: (1) beating heart group: 20 cases of MVR with beating heart under mild hypothermia and CPB; (2) heart arrest group: 20 cases of MVR with heart arrest by using cold blood cardioplegia (CBC) and CPB. Samples of myocardium were obtained at 3 times points during CPB, and myocardial ultrastructure was observed and analysed for both groups. There was no difference in ultrastructure of pre-operation specimens between two groups. Dmit and Amit were higher in arrested heart group than those in beating heart group during operation and after operation, but Vmit, Namit and delta mit were significantly lower in cardiac arrest group than those in beating heart group (P<0.05 or P<0.01). There were no significant differences of Vvmyo between preoperative stage and intraoperative stage (both P>0.05) in both groups, while Vvmyo and delta myo of postoperation stage were significantly lower in heart arrest group than beating heart group (P<0.05 and P<0.01). Beating heart during open-heart surgery is a good method to protect the myocardium being close to physiological condition, and the protective effect may be attributed to alleviation of ischemia/reperfusion injury.


Noteworthy Literature in Cardiac Anesthesia for 2019.
This article represents a selective review of literature published in 2019. Initial results from PubMed searching for a combination of terms, including cardiac anesthesiology and anesthesiology outcomes, yielded more than 1400 publications. From there, we manually screened the results and identified 5 major themes for the year of 2019, including transcatheter techniques, delirium and anesthesiology, coagulation management following cardiopulmonary bypass, perfusion management with del Nido cardioplegia, and applied clinical research. The following research accomplishments have expanded what is possible and set ambitious goals for the future.


The emergence of form by replication.
It is shown with a simple mathematical model that if a system exhibits a given form (a spatial structure) and is put in contact with another system of the same type but in a state of spatial disorder, then under certain conditions their mutual interaction as they evolve in time allows replication of form in the disordered system with a controllable degree of faithfulness.


Atmospheric Oxygen Mediated Radical Hydrothiolation of Alkenes.
A mild, metal-free, atmospheric oxygen-mediated radical hydrothiolation of alkenes (and alkyne) is reported. A variety of sulfur containing motifs including alkanethiols, thiophenols and thioacids undergo an atmospheric oxygen-mediated radical hydrothiolation reaction with a plethora of alkenes in good yield with excellent functional group compatibility, typically with short reaction times to furnish a range of functionalized products. Biomolecules proved tolerant to the conditions and the procedure is robust and easily executable requiring no specialized equipment. Concise mechanistic studies confirm the process proceeds through radical intermediates in a thiol-ene reaction manifold. The methodology offers an efficient "green" approach for thiol-ene mediated "click" ligation and a milder alternative to thermally initiated hydrothiolation processes.


Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice.
The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.


The Effect of Strabismus Muscle Surgery on Corneal Biomechanics.
Studying the early effect of different extraocular muscle (EOM) surgeries on corneal biomechanics. This is a prospective, nonrandomized, interventional study, in which 42 eyes of 29 candidates for EOM surgery for strabismus correction at Cairo university hospitals, aged 14-37 years, were recruited. All participants had measuring of the visual acuity, refraction (spherical equivalent (SE)), assessment of the EOM motility and muscle balance, sensory evaluation, fundus examination, and assessing the ocular biomechanics using the Ocular response analyzer (ORA, Reichert, INC., Depew, NY) noting the corneal hysteresis (CH) and corneal resistance factor (CRF) preoperatively. Same patients were reassessed using ORA 4 weeks postoperatively following a different standard EOM surgery (recti weakening/strengthening and inferior oblique weakening either (graded recession) according to the surgical indication, and ∆CH and ∆CRF were calculated, each is the preoperative - the postoperative value. ∆CH and ∆CRF = -0.78 ± 1.56 and -0.72 ± 2.15, respectively, and a highly significant difference was found between each of the pre- and postoperative CH and CRF (p < 0.001). 18 eyes had single EOM surgery, while 24 had multiple (2 or 3) EOM surgery; ∆CH in the single group = -1.28 ± 1.5, and ∆CH in the multiple group = 0.4 ± 1.49 (p=0.07). 23 eyes had EOM weakening surgery, while 18 had combined weakening and strengthening EOM surgery: ∆CH in the weakening group = -1.24 ± 1.77 and ∆CH in combined group = -0.26 ± 1.07 (p=0.04). A nonsignificant difference was found for ∆CRF (p=0.53). A different EOM surgery has an early tendency for increase of the postoperative CH specially for muscle weakening procedures (recti recession/inferior oblique muscle weakening).


Is it necessary to adjust current creatine kinase reference ranges to reflect levels found in professional footballers?
We aimed to explore the validity of applying current reference ranges of the enzyme creatine kinase (CK) when analysing the medical status of professional footballers and to offer a more functional CK reference range for professional footballers. A sample of 27 professional male footballers competing in The Football League Championship was analysed. The single sample Wilcoxon signed-rank test was used to compare the CK distribution of the study group with that of a control group of military personnel reported in the literature. The median values for study group and the published control group were 284 U/L and 124 U/L, respectively (P<0.001) suggesting that the average CK activity of professional footballers is higher than that of the normal healthy military population. Ethnicity, sex, age and physical exercise are factors that likely influence CK levels among various populations. From our analysis, we recommend a new 95% reference interval of 64.9 U/L to 1971.7 U/L for professional footballers.