Pharmaceutical quality of different Ginkgo biloba brands.
Ginkgo biloba-containing brands are one of the top sellers within the growing market for herbal remedies in many European countries as well as in the USA. In the consumers' interest, these brands should feature a certain quality and should be transparent in quality claims. In this investigation, a variety of products on the USA market was studied with respect to pharmaceutical quality, such as quantity of constituents and in-vitro dissolution. In terms of the content of active substances, flavone glycosides ranged from 24% to 36% and terpene lactones from 4% to 11%. With ginkgolic acids, there was a very large range, from < 500 ppm to about 90000 ppm. Comparing the dissolution rates of terpene lactones and flavone glycosides within the single products, most were approximately the same. Thus, terpene lactones and flavone glycosides were released from these products and dissolved at the same rate in most cases. Furthermore, most of the products investigated released more than the required 75% of the content of both components within 30 min. However, several products showed clear and relevant differences in dissolution rates to the rest (e.g. < 75% within 30 min or even less than 25% after 60 min in one case, indicating much poorer pharmaceutical quality). Beside the comparability respectively standardisation of the extracts used, the in-vitro dissolution of the relevant constituents should be similar to other drugs to guarantee comparable in-vivo performance of herbal products. An important step in standardising pharmaceutical quality is the pharmacopoeial monograph for Ginkgo biloba extract in Germany, standardising the content of pharmacologically relevant substances (flavone glycosides 22-27% and terpenlactones 5-7%, 2.8-3.4% ginkgolides A, B, C and 2.6-3.2% bilobalide thereof). Many of the investigated products, which refer to the German Commission E (of the Federal Institute for Drugs and Medicinal Devices) monograph, are not in accordance with this specification. Thus, they can not be considered to be pharmaceutically equivalent.


Evolutionary Story of the Low/Medium-Affinity IgG Fc Receptor Gene Cluster.
Low/intermediate affinity Fc-gamma receptors (FcγR) are crucial for the recognition of immune complexes and IgG-sensitized microorganisms by phagocytic and cytotoxic effector cells. In all mammalian species studied so far, their genes are clustered in a single locus. However, this locus differs between humans and mice, both in the number of genes and the structure/function of the encoded receptors. We show that murine fcgr3 evolved through several steps into FCGR2A, its ortholog, which is specific to primates. One of these steps was the insertion of a retroviral element bringing a new intracellular exon comprising a non-canonical ITAM motif. We also show that the fcgr3-hspa6-fcgr4-fcgr2b module in mammals that has evolved in a FCGR2A-HSPA6-FCGR4-FCGR2B module in primates, was subsequently duplicated in apes through a Non-Allelic Homologous Recombination (NAHR), giving birth to FCGR2C, a hybrid gene between FCGR2B and FCGR2A. The FCGR4 duplication, which occurred simultaneously, eventually resulted in the emergence of FCGR3B, while FCGR3A remained the true FCGR4 ortholog. FCGR2C and FCGR3B, markers of this NAHR, are present in gorillas and chimpanzees, whereas they are absent in orangutans and more distant primates, such as gibbons and macaques. These data need to be taken into account when testing IgG-based therapies in animal species.


A revised technique for extracapsular lens extraction in the rabbit.
The surgical procedure described here for extracapsular lens extraction utilizes a bent 25 gauge needle as an irrigating cystotome , a 100 degrees superior clear corneal incision, a single clean incision of the lens capsule, a muscle hook for expression of the nucleus, no cortical cleanup, and interrupted 9-0 nylon sutures to close the incision. We have found it a simple and effective technique which utilizes inexpensive instruments commonly available in an ophthalmology department or ophthalmic research laboratory.


Double-walled carbon nanotube array for CO2 and SO2 adsorption.
Grand-canonical Monte Carlo simulations and adsorption experiments are combined to find the optimized carbon nanotube (CNT) arrays for gas adsorption at low pressures and 303 K. Bundles of 3D aligned double-walled carbon nanotube (DWCNT) with inner diameter of 8 nm and different intertube distances were made experimentally. The experimental results show that decreasing intertube distance leads to a significant enhancement in carbon-dioxide (CO2) adsorption capacity at 1 bar. The molecular simulation study on CO2 adsorption onto bundles of 3D aligned DWCNT with inner diameters of 1, 3, and 8 nm and intertube distance of 0-15 nm shows that the intertube distance plays a more important role than the CNT diameter. The simulation results show that decreasing the intertube distance up to 1 nm increases the excess adsorption generally in all the studied systems at pressures 0 < p < 14 bars (the increase can be up to ∼40% depending on the system and pressure). This is in agreement with the experimental result. Further reduction in intertube distance leads to a decrease in the excess adsorption in the pressure range 9 < p < 14 bars. However, at lower pressure, 0 < p < 9 bars, intertube distance of 0.5 nm is found to have the highest excess adsorption. This result is indifferent to tube diameter. Furthermore, molecular simulations are conducted to obtain the optimal parameters, for the DWCNT bundle, for SO2 adsorption, which are similar to those observed for CO2 in the pressure range 0 < p < 3 bars.


Modal compensation of atmospheric turbulence induced wave front aberrations.
A power spectral density method for calculating the efficiency of modal compensation of wave front phase error caused by propagation through atmospheric turbulence is presented. The method permits an accurate evaluation of the interactive effects of isoplanatism, outer and inner scale size, control algorithm, servo type, and order of modal compensation on control loop bandwidth requirements. Applications of the method to some typical ground-to-ground and ground-to-space geometries are presented. Anisoplanatism is shown to limit the amount of compensation possible with adaptive optics, particularly in the higher-order aberration modes.


Zinc deficiency in patients with persistent viral warts.
To determine the association of low serum zinc levels with persistent, progressive or recurrent viral warts. A comparative study. Dermatology outpatient department of Combined Military Hospital, Abbottabad in collaboration with Department of Chemical Pathology, Army Medical College, Rawalpindi, from June 2006 to May 2007. Seventy five patients having warts of more than six months duration, more than 10 in number, who either not responded to or had recurrence after previous treatments for viral warts and not having other chronic dermatological or systemic illness were included in the study after informed consent. Seventy five age and gender matched healthy individuals were taken as control. Serum zinc analysis was carried out by atomic absorption spectrometry using Perkin elmen (USA) apparatus. Independent sample t-test was used to compare mean zinc levels in microgram/litre with significance at p < 0.05. Age of the patients as well as controls ranged from 12-65 years with a mean of 25.88 + 8.90 years. Serum zinc level was low in 42 (56%) patients and 24 (32%) controls (p=0.003). Among the patients, serum zinc level ranged from 695-1090 micro-gram/litre with a mean of 804.38 + 100.60, whereas the level ranged from 690-1100 microgram/litre with a mean of 836.17 + 91.04 among controls (p 0.044). Zinc deficiency is associated with persistent, progressive or recurrent viral warts in the studied patients. Randomized controlled trials with careful dose adjustment of oral zinc sulphate may be helpful to formulate guide lines to manage such patients.


Percutaneous root osteotomy for correction of the deviated nose.
This study describes the use of percutaneous root osteotomy near the intercanthal level for correction of deviated noses. This procedure provides complete mobilization of the midline bony septum. The study analyzed outcomes in patients undergoing this procedure. The study retrospectively reviewed 50 patients who underwent corrective rhinoplasty involving a percutaneous root osteotomy. Two independent rhinoplastic surgeons assessed treatment outcomes by comparing pre- and postoperative photographs. Complications associated with the procedure were assessed also. Postoperative photographs showed the outcome was excellent in 42 cases (84%), good in 2 cases (4%), fair in 4 cases (8%), and no change in the "central area" in 2 cases (4%). No cases showed a poor or worsening outcome, and there were no complications such as visible scarring or osteotomy site depressions. Percutaneous root osteotomy appears to be a valuable adjunct procedure for correction of deviated noses.


Macrocephaly and sclerosis of the tubular bones in an isolated patient: a mild case of craniodiaphyseal dysplasia?
We report a 56-year-old woman, mainly suffering from painful legs and the inability to run. Radiologically, marked sclerosis and hyperostosis of the skull bones is present resulting in macrocephaly. Most tubular bones of the limbs, as well as the clavicles, are affected by sclerosis. By mutation analysis of the TGFB1, SOST and LRP5 genes, we were able to exclude the diagnoses of Camurati-Engelmann disease, Van Buchem disease, sclerosteosis, high-bone-mass trait and endosteal hyperostosis (Worth type). We believe this patient represents one of the very few examples of adult craniodiaphyseal dysplasia with a mild form of the disease and moderate facial changes.


Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice.
High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard (HFL) or palm oil (HFP), or low-fat diet (LFD) for 5weeks. Fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus muscles were characterized with respect to contractile function and selected biochemical features. In FT EDL muscle, a 30%-50% increase in fatty acid (FA) content and doubling of long-chain acylcarnitine (C14-C18) content in response to HFL and HFP feeding were accompanied by increase in protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial oxidative phosphorylation complexes and acyl-CoA dehydrogenases involved in mitochondrial FA β-oxidation. Peak force of FT EDL twitch and tetanic contractions was unaltered, but the relaxation time (RT) of twitch contractions was 30% slower compared to LFD controls. The latter was caused by accumulation of lipid intermediates rather than changes in the expression levels of proteins involved in calcium handling. In ST soleus muscle, no evidence for lipid overload was found in any HFD group. However, particularly in HFP group, the peak force of twitch and tetanic contractions was reduced, but RT was faster than LFD controls. The latter was associated with a fast-to-slow shift in troponin T isoform expression. Taken together, these data highlight fiber-type-specific sensitivities and phenotypic adaptations to dietary lipid overload that differentially impact fast- versus slow-twitch skeletal muscle contractile function.


Linking Complement Activation, Coagulation, and Neutrophils in Transplant-Associated Thrombotic Microangiopathy.
Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe and life-threatening complication of hematopoietic cell transplantation (HCT) that often coincides with graft-versus-host-disease (GVHD). Although endothelial damage seems to be the common denominator for both disorders, the role of complement system, neutrophils, and coagulation has not been clarified. In an effort to distinguish the pathogenesis of TA-TMA from GVHD, we evaluated markers of complement activation, neutrophil extracellular trap (NET) release, endothelial damage, and activation of coagulation cascade in the circulation of patients with these two disorders, as well as control HCT recipients without TA-TMA or GVHD. We observed that the terminal complement product C5b-9 levels, the levels of markers of NET formation, and thrombin-antithrombin complex levels were significantly increased in the TA-TMA group compared with patients without complications, whereas there was no significant difference between the GVHD and the control group. On the other hand, the levels of circulating thrombomodulin, an endothelial damage marker, were significantly increased in both TA-TMA and GVHD patients. These findings propose a role for the interplay between complement system, neutrophil activation through NET release, and activation of the coagulation cascade in TA-TMA.


Communicating effectively with patients suspected of having bulimia nervosa.
The dental team often is confronted with the clinical appearance of erosion affecting the hard and soft oral tissues. An investigative process often is needed to determine the cause of such erosion, because factors other than eating disorders may be involved. The authors present a protocol that should be considered in the assessment of dental erosion. Guidelines provide direction for the clinician toward opening a dialogue with a patient when the suspected cause of erosion is an eating disorder. The authors review publications related to the causes of dental erosion and the patterns that are involved with both chemical and mechanical destruction of oral tissues. They also discuss the oral-tissue effects related to eating disorders. The authors stress the importance of assisting parents in obtaining adequate treatment for pediatric patients. Cases of eating disorders among female college students, athletes, preadolescent children and men are well-documented. However, dental staff members often do not feel comfortable beginning a dialogue with patients who are suspected of having an eating disorder. This article focuses on the proper protocol for approaching such patients and beginning a dialogue. In addition, the authors provide suggestions for limiting further erosive damage to the tissues. They also discuss other causes of erosion that should be considered when assessing any type of oral erosion. The dental team is in a prime position to assist patients who have eating disorders. Timely treatment by mental health and other medical professionals is crucial. The authors suggest a dialogue for approaching these patients and offer educational material to reduce further tissue destruction.


Effect of suicidality on clinical and behavioural outcomes in HIV positive adults in Uganda.
Suicidality is a risk of a person committing suicide often characterized by suicidal ideation, intent or attempts. Despite the high burden of suicidality among individuals living with HIV and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4 counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV Medications). Cross-sectional investigations of these associations are often complicated by bidirectional causal relationships and hence the need for longitudinal study designs. We conducted a cohort study to determine the impact of suicidality on clinical and behavioural outcomes among adults living with HIV/AIDS in Uganda. We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda. Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to determine the relationship between suicidality and indices of HIV outcomes. Majority of the participants were female and the participant mean age was 35 years. Most of them (73%) had primary or no formal education. The proportion of participants with suicidality decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the investigated clinical and behavioural outcomes, baseline suicidality only had a negative impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI 2.45-27.71, p>0.01) times higher for participants with suicidality compared to those without suicidality. The following outcomes were not significantly impacted by baseline suicidality: HIV clinical stage, CD4 count and risky sexual behaviour. The fact that baseline suicidality significantly negatively impacted ART adherence calls for the incorporation of psychosocial interventions to target indices of psychological distress such as suicidality to improve HIV related outcomes.


The Landscape of Anthrax Prevention and Control: Stakeholders' Perceptive in Odisha, India.
The prevalence and outbreaks of anthrax are interlinked with the animal-environment-human context, which signifies the need for collaborative, trans-disciplinary and multi-sectoral approaches for the prevention and control of anthrax. In India, there are hardly any shreds of evidence on the role of various stakeholders' on anthrax prevention and control. Therefore, this study addressed the experiences of various stakeholders on anthrax prevention and control strategies in Odisha, India. A qualitative explorative study was carried out using 42 in-depth-interviews among the stakeholders from health, veterinary and general administrative departments from the block, district, and state level. Two major themes emerged: (1) Epidemiological investigation of anthrax in Odisha, India, and (2) Biological and social prevention strategies for anthrax in Odisha, India. The study emphasizes setting up the surveillance system as per standard guideline, and strengthening the diagnostic facility at a regional medical college laboratory to avoid delay. Moreover, it emphasizes step-up inter-sectoral co-ordination, collaboration and sensitization among health, veterinary, forestry, education, nutrition and tribal welfare departments at all levels in order to reduce the prevalence and control the outbreaks of anthrax in Odisha state. It also recommends raising community literacy, in particular on safe carcass disposal, changing behavior on dead-livestock consumption, and compliance with livestock vaccinations.


Rapid diagnosis of pulmonary tuberculosis by mycobacteriophage assay.
We evaluated FASTPlaqueTB, a recently introduced bacteriophage assay for rapid detection of Mycobacterium tuberculosis complex in sputum specimens, using 169 non-duplicate sputum specimens from patients suspected of pulmonary tuberculosis. The results of 160 specimens were analysed. FASTPlaqueTB assay detected tuberculosis in 77% (46/60) of culture-positive cases. Among the AFB smear-positive cases (n = 47) it had a sensitivity of 76% and specificity of 60% while among AFB smear-negative cases (n = 113) its sensitivity and specificity were 78% and 98%, respectively. The overall sensitivity and specificity of the technique were 77% and 96%, respectively, and the positive and negative predictive values were respectively 92% and 87%. The overall efficiency of the test was 89%. Test results were available in 48 h.


Breaking up is hard to count: the rise of divorce in the United States, 1980-2010.
This article critically evaluates the available data on trends in divorce in the United States. We find that both vital statistics and retrospective survey data on divorce after 1990 underestimate recent marital instability. These flawed data have led some analysts to conclude that divorce has been stable or declining for the past three decades. Using new data from the American Community Survey and controlling for changes in the age composition of the married population, we conclude that there was actually a substantial increase in age-standardized divorce rates between 1990 and 2008. Divorce rates have doubled over the past two decades among persons over age 35. Among the youngest couples, however, divorce rates are stable or declining. If current trends continue, overall age-standardized divorce rates could level off or even decline over the next few decades. We argue that the leveling of divorce among persons born since 1980 probably reflects the increasing selectivity of marriage.


A simple system for studying antibiotic binding to leukocytes.
Studies on the interaction between antibiotics and polymorphonuclear leukocytes (PMLs) usually require the availability of radiolabeled antibiotic, that the antibiotic kill intraleukocyte pathogens, or that the antibiotic affect some function of the leukocyte. The system described here does not have the requirements above but depends instead upon anti-staphylococci activity. The key features of the system are that, following incubation, extracellular antibiotic was removed from PMLs by centrifugation, contact between Staphylococcus aureus 502A and the phagocyte-antibiotic complex was assured by centrifugation at 4 degrees C in 96 well tissue culture dishes, phagocytosis was induced by incubation at 37 degrees C, and assessment of surviving bacteria was accomplished by collecting [3H]thymidine labeled bacteria using a cell harvester. Antibiotics that were active in this system included naphthalenic ansamycins (rifamycins and streptovaricins ), lincosaminides ( clindamycins and pirlimycins ), coumarins (novobiocin), erythromycin, tetracycline, tyrocidine and paulomycin .


Comparison of combitube, easy tube and tracheal tube for general anesthesia.
The Combitube(®) and EasyTube™ enable effective ventilation whether placed in the trachea or esophagus and can be used in prehospital settings, as well as in "Cannot Ventilate Cannot Intubate" situations in the operating room. Whether they can be continued to provide general anesthesia, if required, is not established. Thus the efficacy of Combitube and EasyTube was evaluated and compared with the tracheal tube for general anesthesia using controlled ventilation. Combitube, EasyTube and tracheal tubes were used in 30 patients each to secure the airway in a randomized controlled manner. Ventilatory parameters were measured along with hemodynamic variables, and characteristics related to device placement. There was no significant difference in the various ventilatory parameters including minute ventilation requirement to maintain eucapnia amongst the three groups at any time point. There was no hypoxia or hypercarbia in any patient at any time. Placement of EasyTube was more difficult (P = 0.01) as compared with both Combitube and tracheal tube. EasyTube and Combitube resulted in higher incidence of minor trauma than with a tracheal tube (P = 0.00). Combitube and EasyTube may be continued for general anesthesia in patients undergoing elective nonlaparoscopic surgeries of moderate duration, if placed for airway maintenance. Given the secondary observations regarding placement characteristics of the airway devices, it, however cannot be concluded that the devices are a substitute for endotracheal tube for airway maintenance per se, unless specifically indicated.


Prediction of low Apgar score at five minutes following labor induction intervention in vaginal deliveries: machine learning approach for imbalanced data at a tertiary hospital in North Tanzania.
Prediction of low Apgar score for vaginal deliveries following labor induction intervention is critical for improving neonatal health outcomes. We set out to investigate important attributes and train popular machine learning (ML) algorithms to correctly classify neonates with a low Apgar scores from an imbalanced learning perspective. We analyzed 7716 induced vaginal deliveries from the electronic birth registry of the Kilimanjaro Christian Medical Centre (KCMC). 733 (9.5%) of which constituted of low (< 7) Apgar score neonates. The 'extra-tree classifier' was used to assess features' importance. We used Area Under Curve (AUC), recall, precision, F-score, Matthews Correlation Coefficient (MCC), balanced accuracy (BA), bookmaker informedness (BM), and markedness (MK) to evaluate the performance of the selected six (6) machine learning classifiers. To address class imbalances, we examined three widely used resampling techniques: the Synthetic Minority Oversampling Technique (SMOTE) and Random Oversampling Examples (ROS) and Random undersampling techniques (RUS). We applied Decision Curve Analysis (DCA) to evaluate the net benefit of the selected classifiers. Birth weight, maternal age, and gestational age were found to be important predictors for the low Apgar score following induced vaginal delivery. SMOTE, ROS and and RUS techniques were more effective at improving "recalls" among other metrics in all the models under investigation. A slight improvement was observed in the F1 score, BA, and BM. DCA revealed potential benefits of applying Boosting method for predicting low Apgar scores among the tested models. There is an opportunity for more algorithms to be tested to come up with theoretical guidance on more effective rebalancing techniques suitable for this particular imbalanced ratio. Future research should prioritize a debate on which performance indicators to look up to when dealing with imbalanced or skewed data.


Statistical approaches for evaluating body composition markers in clinical cancer research.
The term 'morphomics' stands for the markers of body composition in muscle and adipose tissues. in recent years, as part of clinical cancer research, several associations between morphomics and outcome or toxicity were found in different treatment settings leading to a growing interest. we aim to review statistical approaches used to evaluate these markers and suggest practical statistical recommendations. Area covered: We identified statistical methods used recently to take into account properties of morphomics measurements. We also reviewed adjustment methods on major confounding factors such as gender and approaches to model morphomic data, especially mixed models for repeated measures. Finally, we focused on methods for determining a cut-off for a morphomic marker that could be used in clinical practice and how to assess its robustness. Expert commentary: From our review, we proposed 13 key points to strengthen analyses and reporting of clinical research assessing associations between morphomics and outcome or toxicity.


Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review.
The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research. Our 2014-2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes. Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23-0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09-0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation. Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need for data that directly compare benefits and harms.


Informed consent in European multicentre randomised clinical trials--are patients really informed?
This study was designed to examine the standard of consent used by investigators in European randomised clinical trials (RCT). The participants of 12 multicentre RCTs published in the European Journal of Cancer in the years 1990-1992 were asked to complete a short questionnaire regarding their practice of obtaining consent in the trial reported. Anonymity was assured. Replies were received from 60 of 88 clinicians contacted. Data showed that 12% of clinicians did not inform their patients about the trial prior to randomisation. Thirty-eight per cent of clinicians did not always tell patients that they had been assigned to their treatment randomly. Only 32% of clinicians used written consent, 21% used written information without obligatory signing, 42% used verbal consent, and in 5% no consent was sought. Even when information was given, only 58% of clinicians gave full information on all aspects of the trial and 42% gave information on the proposed treatment arm only (27% revealing inclusion in an RCT). When examined by geographical origin, clinicians in northern Europe were more likely to obtain full consent than those from southern Europe. Similarly, the level of consent was higher in trials of supportive care than in trials testing curative or palliative antitumour therapies.


Emergency Neurological Life Support: Airway, Ventilation, and Sedation.
Airway management and ventilation are central to the resuscitation of the neurologically ill. These patients often have evolving processes that threaten the airway and adequate ventilation. Furthermore, intubation, ventilation, and sedative choices directly affect brain perfusion. Therefore, airway, ventilation, and sedation was chosen as an emergency neurological life support protocol. Topics include airway management, when and how to intubate with special attention to hemodynamics and preservation of cerebral blood flow, mechanical ventilation settings, and the use of sedative agents based on the patient's neurological status.


[Influence of dopamine on the pulmonary pressure and shunt volume after cardiac surgery (author's transl)].
After the administration of Dopamine to 20 patients after cardiac surgery pulmonary shunt volume was determined with regard to the cardiac output and pulmonary pressure. It was shown that the infusion of Dopamine leads to decrease of the arterio-venous oxygen difference (AVDO2) as well as to the decrease of the PO2 in the arterial blood. On the contrary, in venous bood, PO2, Oxygen saturation, content and pulmonary pressure increased. The increase of the pulmonary right-to-left shunt observed (Qs Qt form 14.9 to 19.2%) is in proportion with the increase in cardiac output. Hence we do not suppose a specific shunting effect of Dopamine. Our findings suggest, that in the case of an already reduced blood oxygen level a further fall of the arterial oxygen saturation caused by a shunt must be avoided by additional enrichment of oxygen content of the inspired air.


Patient satisfaction, safety and efficacy of nurse-led compared to physician-led implantation of cardiac monitors.
Implantation of an implantable cardiac monitor (ICM) is a simple procedure, but adds significant and increasing workload to the arrhythmia service. In 2020, we established a nurse-led ICM implantation service. We aimed to analyze patient satisfaction, adverse events during implant and ICM re-interventions with nurse-led ICM implantation (N-Implant) compared to physician-led ICM implantation (P-Implant). From January 2020 to December 2021 we included all consecutive patients implanted with an ICM in a prospective registry. We collected data on patient characteristics, implant procedure and follow-up. Patients were interviewed by phone four weeks after ICM implantation.Of 321 patients implanted with an ICM (median age 67 years; 33% women), 189 (59%) were N-Implants. More N-Implants were performed in the outpatient clinic compared to P-Implants (95% vs. 8%; p<0.001). Two N-Implant patients experienced vaso-vagal reaction during implantation (1%), whereas no adverse events occurred during P-Implant (p=0.51). 297 patients (93%) completed the questionnaire. Duration of pain was shorter and wound closure after 2 weeks better following N-Implant (p=0.019 and p=0.018). A minor bruise or swelling at the implant site was reported more frequently after N-Implant (p=0.003 and p=0.041). Patient satisfaction was excellent with both N-Implant and P-Implant (99% and 97%; p=0.16). After a median follow-up of 242 days (range 7-725 days), five ICMs (2%) were explanted prematurely, without differences among groups. Reasons for premature explants were local discomfort (n=2), infection, MRI and ICM malfunction. Nurse-led ICM implantation has excellent patient satisfaction without compromising safety. N-Implant both expands nursing competencies and reduces physician workload.


Rosai-Dorfman disease manifesting as a mediastinal mass with calcifications.
Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare entity predominantly affecting children and young adults, characterized in 95% of patients by painless bilateral cervical limphadenopathy. We report the case of a 30-year-old female with an anterior mediastinal mass due to lymph node enlargement, which showed calcifications on computed tomography. To our knowledge, calcification in lymphadenopathy, as is present in this case, has never been described in Rosai-Dorfman disease.


Coping strategies and belief in COVID-19 conspiracy theories.
Conspiracy beliefs have been related to aversive emotional experiences often accompanying major world events and have also been linked to maladaptive ways of coping with stress. In this research, we examined how different coping strategies (i.e. self-sufficient, social-support, avoidance and religious) predicted the adoption of COVID-19 conspiracy theories. In two studies (Study 1, n = 1000 and Study 2, n = 616) conducted among Polish participants, we found that avoidance and religious coping were positively linked to COVID-19 conspiracy beliefs. In Study 1, conspiracy beliefs also mediated the positive relationships between avoidance and religious coping and adherence to safety and self-isolation guidelines during the COVID-19 pandemic. Study 2 additionally showed that the relationship between fear, induced by reading threatening news on COVID-19, and conspiracy beliefs was the strongest among those high in avoidance coping. These studies highlight the role of coping strategies in the adoption of COVID-19 conspiracy beliefs.


A role for RASSF1A in tunneling nanotube formation between cells through GEFH1/Rab11 pathway control.
By allowing intercellular communication between cells, tunneling nanotubes (TNTs) could play critical role in cancer progression. If TNT formation is known to require cytoskeleton remodeling, key mechanism controlling their formation remains poorly understood. The cells of human bronchial (HBEC-3, A549) or mesothelial (H2452, H28) lines are transfected with different siRNAs (inactive, anti-RASSF1A, anti-GEFH1 and / or anti-Rab11). At 48 h post-transfection, i) the number and length of the nanotubes per cell are quantified, ii) the organelles, previously labeled with specific tracers, exchanged via these structures are monitored in real time between cells cultured in 2D or 3D and in normoxia, hypoxia or in serum deprivation condition. We report that RASSF1A, a key-regulator of cytoskeleton encoded by a tumor-suppressor gene on 3p chromosome, is involved in TNTs formation in bronchial and pleural cells since controlling proper activity of RhoB guanine nucleotide exchange factor, GEF-H1. Indeed, the GEF-H1 inactivation induced by RASSF1A silencing, leads to Rab11 accumulation and subsequent exosome releasing, which in turn contribute to TNTs formation. Finally, we provide evidence involving TNT formation in bronchial carcinogenesis, by reporting that hypoxia or nutriment privation, two almost universal conditions in human cancers, fail to prevent TNTs induced by the oncogenic RASSF1A loss of expression. This finding suggests for the first time that loss of RASSF1A expression could be a potential biomarker for TNTs formation, such TNTs facilitating intercellular communication favoring multistep progression of bronchial epithelial cells toward overt malignancy.


[Experience in treating patients with tuberculous spondylitis].
Some experience in treating 144 patients with tuberculous spondylitis is presented. The cervical, thoracic, and lumbar parts of the spine were affected in 12, 83, and 49 patients, respectively. Medical and surgical treatment was performed in 82 (57%) and 62 (43%) patients, respectively. The medical treatment included the use of antituberculous drugs, pathogenetic exposures, and an orthopedic regimen. The surgical treatment was a stage of multimodality therapy in 62 patients and it involved the radical elimination of a specific inflammation focus, followed by bone defect replacement and vertebral ceramic implant stabilization. The long-term results were studied in the periods of 2 to 10 years. All the patients were found to have a formed osseous block: exacerbations and recurrences being absent.


Morphology of intestinal villi in African antelope (Artiodactyla: Bovidae).
Villous morphology in 16 species of African antelope varied from finger-like and leaf-like to ridge-like forms. Some species showed uniform villi whereas it was variable in others. There was a slight indication that leaf-like and finger-like forms become more frequent in the distal regions of the small intestine. The variation in morphology was not associated with body size or phylogeny, but did show a significant correlation with diet: species with high moisture content and/or high fibre levels (equivalent to low bulk values) in the digesta were more likely to have ridges, which were the lowest of the villi.


Estimation of fluorescence-tagged RNA numbers from spot intensities.
Present research on gene expression using live cell imaging and fluorescent proteins or tagged RNA requires accurate automated methods of quantification of these molecules from the images. Here, we propose a novel automated method for classifying pixel intensities of fluorescent spots to RNA numbers. The method relies on a new model of intensity distributions of tagged RNAs, for which we estimated parameter values in maximum likelihood sense from measurement data, and constructed a maximum a posteriori classifier to estimate RNA numbers in fluorescent RNA spots. We applied the method to estimate the number of tagged RNAs in individual live Escherichia coli cells containing a gene coding for an RNA with MS2-GFP binding sites. We tested the method using two constructs, coding for either 96 or 48 binding sites, and obtained similar distributions of RNA numbers, showing that the method is adaptive. We further show that the results agree with a method that uses time series data and with quantitative polymerase chain reaction measurements. Lastly, using simulated data, we show that the method is accurate in realistic parameter ranges. This method should, in general, be applicable to live single-cell measurements of low-copy number fluorescence-tagged molecules. MATLAB extensions written in C for parameter estimation and finding decision boundaries are available under Mozilla public license at http://www.cs.tut.fi/%7ehakkin22/estrna/ CONTACT: firstname.lastname@example.com.


The role of polyethylene wear in joint replacement failure.
Aseptic loosening is the major cause of failure of joint replacement prostheses. Polyethylene implants removed at revision surgery regularly show wear. It is proposed that the polyethylene particles released into the tissues as a consequence of this wear induce a tissue response that precedes aseptic loosening. This paper presents the results of recent in vivo and in vitro studies of the biological response to polyethylene wear particles undertaken in the authors' laboratories. A clinical perspective is provided by the inclusion of the authors' recent observations of retrieval analyses of joint replacement implant wear and the tissue response to polyethylene in humans.


Shrinking tropical forests, human agents of change, and conservation policy.
Human agents of landscape transformation in the tropics affect forests differently as the forests decline in size. Five agents of change--road builders, corporate concession holders, community forest managers, park advocates, and urban consumers--have different effects on large forests in remote tropical regions than they do on remnant forests in settled agricultural regions. Because forests vary so much in size across tropical regions, these differences in the effects of agents on forests have important implications for regional conservation efforts. To make these implications explicit, I compared the effects of the five agents in regions with large forests with their effects in regions with small forests. The comparisons indicated that, as forests declined in size, new roads no longer destroyed forests, corporate loggers left the forests, community forest managers became more effective, parks became less feasible as a means of conservation, and urban consumers initiated tree planting. My results suggest that awareness about the changing effects of humans on landscapes with shrinking forests can serve as a useful tool in formulating regionally appropriate policies for conserving tropical forests.


Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial.
Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition. We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls. In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome. Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment. Bill & Melinda Gates Foundation; Médecins sans Frontières Operational Center Paris; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Edward Mallinckrodt Jr Foundation; Doris Duke Foundation.


The incidence of carcinoma in the gastric remnant after resection for benign ulcer disease.
During the period 1950-1953, gastric resection was performed on 569 patients for benign ulcer disease at the Serafimer Hospital, Stockholm, Sweden. The purpose of this investigation uas to assess the incidence of cancer and precancerous lesions in the gastric remnant. There were 15 postoperative deaths. 223 patients when traced were dead, and in 130 of these follow-up was adequate. Two cases with carcinoma in the gastric remnant were found among these. 72 patients were lost from follow-up. 253 patients when traced were alive, and in 111 of these, endoscopy and biopsy have been performed. In one patient there was a severe dysplasia but no invasive carcinomas were found. 130 dead patients and 111 living patients have been adequately followed after gastric resection for benign ulcer disease. Two carcinomas were found which makes the incidence 0,8%.


Scattering of on-axis Gaussian beam by a uniaxial anisotropic object.
Based on the extended boundary condition method, a semi-analytical solution to the scattering of an on-axis Gaussian beam by an arbitrarily shaped uniaxial anisotropic object is constructed. For the on-axis incident Gaussian beam, scattered fields as well as internal fields are expanded in terms of appropriate spherical vector wave functions, and the unknown expansion coefficients of the scattered fields are determined by using Schelkunoff's equivalence theorem and continuous boundary conditions. Numerical results of the normalized differential scattering cross section are presented, and the scattering characteristics are discussed concisely.


Localized eosinophilic gastroenteritis with necrotizing granulomas presenting as acute abdomen.
Eosinophilic gastroenteritis is a condition of unknown aetiology that has been frequently reported involving the stomach and bowel. The colon is rarely cited as a site for the condition. We report a patient suffering from allergic symptoms (asthma, atopic dermatitis, elevated serum IgE levels) who presented with colonic perforation due to eosinophilic colitis with necrotizing granulomas.


A SWOT (Strengths, Weaknesses, Opportunities, and Threats) Analysis of ChatGPT in the Medical Literature: Concise Review.
ChatGPT is a 175-billion-parameter natural language processing model that is already involved in scientific content and publications. Its influence ranges from providing quick access to information on medical topics, assisting in generating medical and scientific articles and papers, performing medical data analyses, and even interpreting complex data sets. The future role of ChatGPT remains uncertain and a matter of debate already shortly after its release. This review aimed to analyze the role of ChatGPT in the medical literature during the first 3 months after its release. We performed a concise review of literature published in PubMed from December 1, 2022, to March 31, 2023. To find all publications related to ChatGPT or considering ChatGPT, the search term was kept simple ("ChatGPT" in AllFields). All publications available as full text in German or English were included. All accessible publications were evaluated according to specifications by the author team (eg, impact factor, publication modus, article type, publication speed, and type of ChatGPT integration or content). The conclusions of the articles were used for later SWOT (strengths, weaknesses, opportunities, and threats) analysis. All data were analyzed on a descriptive basis. Of 178 studies in total, 160 met the inclusion criteria and were evaluated. The average impact factor was 4.423 (range 0-96.216), and the average publication speed was 16 (range 0-83) days. Among the articles, there were 77 editorials (48,1%), 43 essays (26.9%), 21 studies (13.1%), 6 reviews (3.8%), 6 case reports (3.8%), 6 news (3.8%), and 1 meta-analysis (0.6%). Of those, 54.4% (n=87) were published as open access, with 5% (n=8) provided on preprint servers. Over 400 quotes with information on strengths, weaknesses, opportunities, and threats were detected. By far, most (n=142, 34.8%) were related to weaknesses. ChatGPT excels in its ability to express ideas clearly and formulate general contexts comprehensibly. It performs so well that even experts in the field have difficulty identifying abstracts generated by ChatGPT. However, the time-limited scope and the need for corrections by experts were mentioned as weaknesses and threats of ChatGPT. Opportunities include assistance in formulating medical issues for nonnative English speakers, as well as the possibility of timely participation in the development of such artificial intelligence tools since it is in its early stages and can therefore still be influenced. Artificial intelligence tools such as ChatGPT are already part of the medical publishing landscape. Despite their apparent opportunities, policies and guidelines must be implemented to ensure benefits in education, clinical practice, and research and protect against threats such as scientific misconduct, plagiarism, and inaccuracy.


Tricuspid endocarditis with ventricular septal defect. Case report with surgical management.
A 13-year-old girl presented with infective endocarditis of the tricuspid valve related to a residual ventricular septal defect. Antibiotic therapy produced a satisfactory initial improvement, however, subsequent deterioration with uncontrolled infection, in spite of alterations in the antibiotic regime, necessitated surgical intervention. Because the endocarditis was localized to the septal leaflet, management by excision of this leaflet and annuloplasty was possible and resulted in a rapid and sustained clinical improvement with no evidence of significant residual valvar incompetence. The medical management of infective endocarditis requires bacteriological assessment to ensure that the drugs and dosages selected are appropriate and adequate for the causative organism. Early operation may be required for uncontrolled infection or cardiac decompensation; in tricuspid endocarditis secondary to a ventricular septal defect, the operation described permits removal of infective tissue while retaining valvar competence.


The adult coeliac ganglion: a morphologic study.
The coeliac plexus is located on the sides of the coeliac trunk and nearby the origins of the superior mesenteric and renal arteries. Afferent branches get to this plexus from the vagus nerve, splanchnic nerves and the right phrenic nerve; efferents leave for viscera through periarterial plexuses and the retroportal nerves. The coeliac plexus ganglia - coeliac, superior mesenteric, aorticorenal - are prevertebral ganglia that receive the preganglionic sympathetic fibers brought by the splanchnic nerves from the thoracic spinal cord. For studying the adult coeliac ganglia dissections were performed then pieces were drawn for silver staining by the method of Bielschowsky on blocks and HE stains. The adult coeliac ganglia consist of well-defined ganglionic subunits, of a varying number of neurons with somata ranging from 14 to 48 microns and characteristically involved in extensive dendritic fields. Individual degrees of coalescence may justify the macroscopic appearance of the coeliac ganglion but its structure keeps distinctive subunits.


[Fever with chemotherapy induced neutropenia].
Cancer patients under chemotherapy are at high risk for neutropenia. If fever occurs in this situation an oncologic emergency is underway. Patient should receive immediate basic diagnostic procedures and broad-spectrum antibiotics have to be initiated. Definition of febrile neutropenia (FN) encloses oral temperature of > 38.3 °C or two consecutive readings of > 38.0 °C one hour apart and an absolute neutrophil count of < 0.5 × 109/l. FN management requires immediate action and therefore needs patient education and standard operating procedures in the clinical setting. Treatment strategies depend on risk factors and symptoms of the patient. Instruments, mainly the Multinational Association for Supportive Care (MASCC), can predict low and high risk situations and are useful tools in clinical practice. Low-risk patients can either be treated by oral or short term intravenous antibacterial therapy with an early change to an oral protocol (oral treatment recommendation: Quinolone with amoxicillin/clavulanic acid). Hospital admission is recommended in low-risk patients but outpatient management has become increasingly appealing in selected cases due to costs, reduction in nosocomial infections and patient's convenience. High-risk patients should always be admitted to the hospital and broad-spectrum intravenous antibiotics should be commenced promptly (intravenous treatment recommendation: anti-pseudomonas cephalosporin. Local epidemiologic bacterial isolate and resistance patterns are important since MRSA or other resistances should be covered). Duration of treatment depends on neutrophil count, patient's symptoms and fever. Evaluation should be done on a daily basis. If fever continues after 48 - 72 hours, antibiotic rotation and/or antifungal therapy may be needed.


Chemoprotective and adjuvant effects of immunomodulator ginsan in cyclophosphamide-treated normal and tumor bearing mice.
Ginsan is a polysaccharide extracted from Panax ginseng that is known to have multiple immunomodulatory effects. This study evaluates the chemoprotective effect of ginsan on normal mice and the adjuvant effect on tumor bearing mice in combination with cyclophosphamide (CP). Ginsan (100 mg/kg) was injected 24 h before or after a sublethal dose of a CP treatment. The mice pre-treated with ginsan all died within 10 days whereas up to 53 percent of the mice post-treated with ginsan increased survival to day 30 compared with only 10 percent in the CP alone treated group on day 30. The post-treatment of ginsan accelerated the recovery of the bone marrow cells and blood neutrophils by approximately 1.3- and 1.75-fold compared to CP treated control mice at 5 days after CP administration, respectively. These marked differences in activity between the pre- and post-treatment of ginsan with CP was clarified by examining the mRNA expression levels of several cytokines in spleen cells and the self-renewal potential of hematopoietic progenitor cells, CFU-s. The post-treatment with ginsan increased the mRNA expression levels of TNF-alpha, IL-1beta, IL-6, SCF, and GM-CSF with respect to that of the CP alone or ginsan pre-treated group. Similarly, the number of CFU-s was significantly higher in the mice post-treated with ginsan. The inhibition of tumor growth and survival elongation was also observed when ginsan was administered 24 h after the CP treatment. These results show that the post-treatment with ginsan had an immunomodulating and adjuvant effect in combination with CP, which indicates its wide applications in reducing the adverse effects of chemotherapy and improving the general conditions of patients.


Does the external appearance of a Meckel's diverticulum assist in choice of the laparoscopic procedure?
In the era of laparoscopic surgery, the resection of a Meckel's diverticulum is a good indication for a laparoscopic procedure. In this paper, the relationship between the distribution of gastric heterotopia (GH) and the external appearance of the diverticulum was studied for the proper choice of the laparoscopic procedure. Symptomatic diverticula containing GH in eight patients were analyzed with regard to the distribution of gastric mucosa and the external appearance. While the long diverticula had the GH at the distal end, in the short diverticula it occurred in almost any area. For long diverticula, simple transverse resection with a stapling device is recommended. However, in short diverticula ileal resection with end-to-end anastomosis or wedge resection after exteriorization is recommended.


Quantification of mitochondrial DNA in heteroplasmic fibroblasts with competitive PCR.
Kearns-Sayre syndrome (KSS) is a disease with severe clinical symptoms that often arises from a mitochondrial DNA deletion of 4977 bp. Quantification of defective mitochondrial DNA is important since the severity of symptoms in KSS is thought to be related to increased content of abnormal mitochondrial DNA. We developed a rapid, quantitative and competitive PCR assay to measure both wild-type and mutant forms of mitochondrial DNA in cells from KSS patients. The assay can accurately measure absolute numbers of mitochondrial DNA per cell by normalizing to a single copy nuclear gene.


Aortic dissection as a rare complication of percutaneous coronary intervention.
Aortic dissection is a rare but life-threatening complication that can occur during percutaneous coronary intervention procedures. We present a case of a 55-year-old woman who underwent a right coronary angioplasty that was complicated by a proximal dissection of the ascending aorta. Urgent surgical repair of the aorta was performed and the patient was discharged in stable clinical condition.


The lens influences aqueous humor levels of transforming growth factor-beta 2.
Transforming growth factor-beta 2 (TGF-beta 2) is a pluripotent cytokine which has been suggested to play a number of roles in ocular physiologic and pathologic states. Intraocular fluid (i.o.f.) levels of TGF-beta 2 are quite high. Although the sources of ocular TGF-beta are not completely defined, the retinal pigment epithelium, the epithelium of the ciliary body and trabecular meshwork cells all secrete it. In this study we utilized canine lens and rabbit ciliary pigmented epithelial cell cultures to quantitate the in vitro secretion of TGF-beta 2. In addition, the effects of aphakia or the presence of cataractous lenses on IOF TGF-beta 2 levels were determined. Lens and ciliary body epithelial cell culture supernatants and aqueous humors were assayed for total TGF-beta 2 levels by ELISA and bioassay. TGF-beta 2 accumulated in the media bathing lens epithelial cell cultures (0.7 +/- 0.03 ng/ml at day 2) and ciliary pigmented epithelial cell cultures (0.8 +/- 0.06 ng/ml at day 2) in a time-dependent manner. Surprisingly, aqueous humor from aphakic rabbit eyes contained significantly higher levels of TGF-beta 2 than their contralateral phakic controls. Furthermore, aqueous humor from canine eyes with cataracts also contained significantly higher levels of TGF-beta 2 than normal eyes. These results suggest that the lens secretes TGF-beta 2 and that the presence and status of the lens may influence IOF TGF-beta 2 levels.


Effect of the variations of female sex hormones during the menstrual cycle upon serum somatomedin and growth-promoting activity.
Serum growth-promoting activity measured upon lymphocytes, sulfation activity and radioimmunoassayable somatomedin C (Sm-C) levels were measured in sera from women during the menstrual cycle. The data showed that: estradiol, progesterone, LH or FSH added in vitro do not increase the 3H-thymidine uptake into lymphocytes; the serum thymidine activity decreases during the luteal stage of the cycle, and is negatively correlated with the progesterone levels; the sulfation factor and Sm-C levels do not have significant variations during the menstrual cycle, and the GH maximum values are attained during the luteal stage.


Giant splenic artery aneurysm treated surgically with spleen and pancreas preservation.
Aneurysms of the splenic artery represent a rare clinical entity, even though they account for 60-70% of all visceral artery aneurysms. Splenic artery aneurysms larger than 5 cm are extremely rare, and they are considered to be giant. Possible causes of splenic artery aneurysm development include: trauma, hormonal and local hemodynamic changes in pregnancy, portal hypertension, arterial degeneration, infection and postsplenectomy occurrence. Surgical treatment of giant splenic artery aneurysms includes procedures that frequently require pancreatectomy and splenectomy. We present a case of a 10.2 cm giant splenic artery aneurysm, firmly adhered to the pancreas, which was treated surgically, with spleen and pancreas preservation. SIMILAR CASES PUBLISHED: Although many cases on treatment of giant splenic artery aneurysm have been published, the majority have described additional visceral resections associated with aneurysmectomy, which is in contrast with our report. Furthermore, aneurysms reaching 10 cm in size were extremely rare.


Bronchodilatory and circulatory effects of inhaling increasing doses of an anti-cholinergic drug, ipratropium bromide (SCH 1000).
Dynamic spirometry with flow-volume curves and measurement of static lung volumes in a body plethysmograph were done in 11 patients with reversible airways obstruction before and up to 240 min after inhalation of 20 mug SCH 1000 and of another 40 mug 60 min later. Forced expiratory volume in 1 s (FEV1), vital capacity (VC) and maximal expiratory flow at 50% VC (V 50% VC) increased successively, reaching maximum after 120 min. In a second part of the study 13 patients inhaled 2+4+8 puffs of SCH 1000 (280 mug in all) at 30-min intervals. PEFR increased significantly up to 224 l/min (44% of predicted normal), with increasing number of SCH 1000 inhalations; no further general effect occurred after additional 3 puffs of terbutaline. Heart rate and blood pressure showed no clinically significant changes. No subjective or objective side-effects were noted.


HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss.
Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the EGF receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTKs) in glioblastoma (GBM). While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate GBM in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival, suggesting that HBEGF may be a clinically relevant target.


Spontaneous aortic dissection in a 14-year-old adolescent.
We describe a case of a 14-year-old boy with a spontaneous aortic dissection. The diagnosis was suspected and confirmed with an urgent transthoracic echocardiogram and computer tomography (CT). He underwent an immediate surgery with tube graft replacement of the ascending aorta using a biological glue to reinforce the distal false lumen. Although the immediate postoperative course was uneventful, he continued to have a persistent distal false lumen, which was observed to be enlarging in size on close follow-up. Potential causes of this complication are discussed along with the various different etiologies for aortic dissection in this rare age group.


Relapse of substance use disorder and its prevention among persons with co-occurring disorders.
This article summarizes the scientific literature on the relapse process, describes the basic principles of relapse prevention treatment, highlights the major empirical studies, and offers suggestions for future research and application, especially in terms of ongoing care for persons with co-occurring disorders. Relapse prevention treatments have a well-established efficacy and effectiveness for persons with substance use disorders. Key ingredients include reducing exposure to substances, fostering motivation for abstinence, self-monitoring, recognizing and coping with cravings and negative affect, identifying thought processes with relapse potential, and deploying, if necessary, a crisis plan. Relapse prevention approaches may be best suited for persons in the action of maintenance stages of treatment or recovery. Further research is needed to examine relapse prevention therapies as a key component to continuing care for persons with co-occurring substance use and psychiatric disorders.


Mobile health technology and the use of health-related mobile applications.
Medical mobile applications (apps) are prevalent in society. Healthcare providers use them to obtain clinical information more efficiently, and healthcare consumers use them to gain greater personal control over their health management. With the increasing number of health-related mobile apps available, people in the oncology community now have many relevant apps at their fingertips. These apps are targeted to the oncology healthcare provider as well as the patient. This article will review a few popular apps and discuss the potential benefits of accessing information using apps and the possible risks associated with them.


Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro.
Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti-inflammatory activity, but the effect of its active metabolite Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) has not been well established. In this study, we investigated the anti-neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS) cells, including microglia (BV-2), astrocytes (C6), and neurons (N2a), were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), Mitogen activated protein kinase (MAPK) signaling proteins, and apoptosis-related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS)-induced TLR4 activation, MAPK activation, NF-kB-mediated transcription of inflammatory mediators, production of nitric oxide (NO), release of prostaglandin E2 (PGE-2), secretion of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), in Lipopolysaccharide (LPS)-activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS-activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF) production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti-neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.


Understanding prevention effectiveness in real-world settings: the National Cross-Site Evaluation of high risk youth programs.
The National Cross-Site Evaluation is a large multisite evaluation (MSE) of 48 substance abuse prevention programs, 5,934 youth participating in programs, and 4,539 comparison youth programs. Data included a self-report questionnaire administered at 4 points in time, detailed dosage data on over 217,000 program contacts, and detailed site visit information. In a pooled analysis, the programs did not demonstrate significant positive effects on a composite outcome measure of tobacco, alcohol, and marijuana use in the previous 30 days. However, disaggregated analyses indicated that 1) sites in which comparison groups had strong opportunity to participate in prevention programs suppressed observed effects; 2) youth who had already started using before they entered programs reduced use significantly more than comparison youth who had started using; and 3) both males and females who participated in programs significantly reduced use relative to comparisons, but in very different patterns. Combining these patterns produced an apparent null effect. Finally, programs that incorporated at least 4 out of 5 effective intervention characteristics identified in the study significantly reduced use for both males and females relative to comparison youth. The lessons produced by this study attest to the value of MSE designs as a source of applicable knowledge about prevention interventions.


Desert Dust as a Source of Iron to the Globally Important Diazotroph Trichodesmium.
The marine cyanobacterium Trichodesmium sp. accounts for approximately half of the annual 'new' nitrogen introduced to the global ocean but its biogeography and activity is often limited by the availability of iron (Fe). A major source of Fe to the open ocean is Aeolian dust deposition in which Fe is largely comprised of particles with reduced bioavailability over soluble forms of Fe. We report that Trichodesmium erythraeum IMS101 has improved growth rate and photosynthetic physiology and down-regulates Fe-stress biomarker genes when cells are grown in the direct vicinity of, rather than physically separated from, Saharan dust particles as the sole source of Fe. These findings suggest that availability of non-soluble forms of dust-associated Fe may depend on cell contact. Transcriptomic analysis further reveals unique profiles of gene expression in all tested conditions, implying that Trichodesmium has distinct molecular signatures related to acquisition of Fe from different sources. Trichodesmium thus appears to be capable of employing specific mechanisms to access Fe from complex sources in oceanic systems, helping to explain its role as a key microbe in global biogeochemical cycles.


Thermodynamics of miracidial survival and metabolism.
Miracidia are short-lived, non-feeding (lecithotrophic) free-living stages of trematodes, whose survival is potentially influenced by temperature. Climate change may result in elevated temperatures affecting trematode transmission. Therefore understanding their thermobiology forms an important step in determining the future dynamics of parasite populations. An empirical relationship exists between the mean expected life span of lecithotrophic larvae and the half life of their population (t(0·5)) and therefore t(0·5) is a good indicator of glycogen utilization. In this study experimental data on the effects of temperature on miracidial survival were compiled from the scientific literature and evaluated in terms of metabolism using Q 10 and Arrhenius activation energy (E* or μ). Temperature poorly influenced survival/metabolism with all miracidia having distinct zone(s) of thermostability. Overall there were few differences in Q(10) and E* values between most species temperature ranges whilst there were only limited strain-specific variations in thermal responses of laboratory-maintained Schistosoma mansoni. Miracidia demonstrated a trend of greater thermal resistance than cercariae. In particular, comparative studies on 4 strains of the same species of miracidia and cercariae showed little correlation in thermal biology between the 2 life-history stages. The importance of these results for trematode transmission under global climate change is discussed.


Effect of increasing age on hemodynamics of spontaneously hypertensive rats.
Arterial pressure, cardiac output, and total peripheral resistance were compared between spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) at 4, 7, and 12 months of age. The rats were anesthetized with pentobarbital sodium, thoracotomized and kept under positive pressure respiration. Cardiac output was measured with an electromagnetic flowmeter probe placed at the ascending aorta. On all the age groups, arterial pressure and total peripheral resistance were significantly higher in SHR than in NCR, while cardiac output per body weight was not different. However, the significant differences in pressure and resistance at each age disappeared after ganglion blockade with hexamethonium bromide. Total peripheral resistance was not higher in SHR than in NCR even after cardiac output, which had once been diminished by blockade, was restored to the pre-blockade level by dextran infusion. Phenoxybenzamine, an alpha adrenergic receptor blocker, also equalized arterial pressure and total peripheral resistance between SHR and NCR, both aged about 10 months, without decrease in cardiac output. It is concluded that, in both young and old SHR's, the hypertensive state is maintained by an increase in total peripheral resistance ascribable to sympathetic activity.


The DNA Exonucleases of Escherichia coli.
DNA exonucleases, enzymes that hydrolyze phosphodiester bonds in DNA from a free end, play important cellular roles in DNA repair, genetic recombination and mutation avoidance in all organisms. This article reviews the structure, biochemistry, and biological functions of the 17 exonucleases currently identified in the bacterium Escherichia coli. These include the exonucleases associated with DNA polymerases I (polA), II (polB), and III (dnaQ/mutD); Exonucleases I (xonA/sbcB), III (xthA), IV, VII (xseAB), IX (xni/xgdG), and X (exoX); the RecBCD, RecJ, and RecE exonucleases; SbcCD endo/exonucleases; the DNA exonuclease activities of RNase T (rnt) and Endonuclease IV (nfo); and TatD. These enzymes are diverse in terms of substrate specificity and biochemical properties and have specialized biological roles. Most of these enzymes fall into structural families with characteristic sequence motifs, and members of many of these families can be found in all domains of life.


Autoradiographic localization of [3H]zolpidem binding sites in the rat CNS: comparison with the distribution of [3H]flunitrazepam binding sites.
The regional distribution of [3H]zolpidem, a novel imidazopyridine hypnotic possessing preferential affinity for the BZD1 (benzodiazepine subtype 1) receptor, has been studied autoradiographically in the rat CNS and compared with that of [3H]flunitrazepam. The binding of [3H]zolpidem to rat brain sections was saturable, specific, reversible, and of high affinity (KD = 6.4 nM). It occurred at a single population of sites whose pharmacological characteristics were similar to those of the benzodiazepine receptors labeled with [3H]flunitrazepam. However, ethyl-beta-carboline-3-carboxylate and CL 218,872 were more potent displacers of [3H]zolpidem than of [3H]flunitrazepam. The autoradiographic brain distribution of [3H]zolpidem binding sites was qualitatively similar to that previously reported for benzodiazepine receptors. The highest levels of [3H]-zolpidem binding sites occurred in the olfactory bulb (glomerular layer), inferior colliculus, ventral pallidum, nucleus of the diagonal band of Broca, cerebral cortex (layer IV), medial septum, islands of Calleja, subthalamic nucleus, and substantia nigra pars reticulata, whereas the lowest densities were found in parts of the thalamus, pons, and medulla. Comparative quantitative autoradiographic analysis of the binding of [3H]zolpidem and [3H]flunitrazepam [a mixed BZD1/BZD2 (benzodiazepine subtype 2) receptor agonist] in the CNS revealed that the relative density of both 3H-labeled ligands differed in several brain areas. Similar levels of binding for both ligands were found in brain regions enriched in BZD1 receptors, e.g., substantia nigra pars reticulata, inferior colliculus, cerebellum, and cerebral cortex lamina IV. The levels of [3H]zolpidem binding were five times lower than those of [3H]flunitrazepam binding in those brain regions enriched in BZD2 receptors, e.g., nucleus accumbens, dentate gyrus, and striatum. Moreover, [3H]zolpidem binding was undetectable in the spinal cord (which contains predominantly BZD2 receptors). Finally, like CL 218,872 and ethyl-beta-carboline-3-carboxylate, zolpidem was a more potent displacer of [3H]flunitrazepam binding in brain regions enriched in BZD1 receptors than in brain areas enriched in BZD2 receptors. The present data add further support to the view that zolpidem, although structurally unrelated to the benzodiazepines, binds to the benzodiazepine receptor and possesses selectivity for the BZD1 receptor subtype.


Posterior microphthalmos, retinitis pigmentosa, and foveoschisis caused by a mutation in the MFRP gene: a familial study.
Background: To characterize the phenotype and genotype of a rare syndrome associating posterior microphthalmos (PM), retinitis pigmentosa (RP), and foveoschisis in a consanguineous Spanish family. Methods: The study involved five family members, consisting of three siblings and their parents. All members underwent comprehensive eye examinations for best corrected visual acuity, axial length and refractive error, electroretinography (ERG), fundus photography, retinal fluorescein angiography (FA), and optical coherence tomography (OCT). Clinical exome sequencing of more than 6,000 clinically relevant genes (SureSelect Focused Exome, Agilent) was performed using the Illumina HiSeq 3000 system. Candidate variants were validated and segregated by Sanger sequencing. Results: The affected siblings had bilateral shortening of the posterior ocular segment and normal anterior segment dimensions. The fundoscopy, ERG, and FA results were compatible with RP. Macular OCT analysis revealed schisis of the outer retinal layer. Our data analysis pipeline identified a homozygous frameshift mutation in exon 5 of the membrane frizzled-related protein (MFRP) gene (c.498delC; p.Asn167Thrfs*25). Conclusion: Our study confirmed the association of PM with RP as an autosomal recessive syndrome. Although this has previously been described, it seems that there are some constant (i.e., PM and RP) and some variable features (i.e., optic nerve drusen and foveoschisis). The MFRP mutation has also been detected in other studies associating PM with RP. Analysis of a larger series of cases at the clinical and genetic levels would certainly help us to better understand the phenotype-genotype correlations of this syndrome.


Hypoglycemia and ventricular tachycardia due to adenocarcinoma of the stomach.
We report the first case of adenocarcinoma of the stomach associated with severe hypoglycemia. Accompanying the profound hypoglycemia, as low as 5 mg per cent by the orthotoluidine method, were multiple episodes of ventricular tachycardia which were abolished by glucose infusion. Following surgical excision of a hemorrhagic portion of the tumor, normoglycemia levels were achieved and ventricular irritability was no longer present. The possible mechanisms of hypoglycemia in extrapancreatic tumors are discussed as well as a mechanism for hypoglycemic-induced ventricular tachycardia. It is postulated that hemorrhage of a necrotic tumor may release large amounts of an insulin-like substance and cause hypoglycemic coma.


Mobile Device Security: Perspectives of Future Healthcare Workers.
Healthcare data breaches on mobile devices continue to increase, yet the healthcare industry has not adopted mobile device security standards. This increase is disturbing because individuals are often accessing patients' protected health information on personal mobile devices, which could lead to a data breach. This deficiency led the researchers to explore the perceptions of future healthcare workers regarding mobile device security. To determine healthcare students' perspectives on mobile device security, the investigators designed and distributed a survey based on the Technology Threat Avoidance Theory. Three hundred thirty-five students participated in the survey. The data were analyzed to determine participants' perceptions about security threats, effectiveness and costs of safeguards, self-efficacy, susceptibility, severity, and their motivation and actions to secure their mobile devices. Awareness of interventions to protect mobile devices was also examined. Results indicate that while future healthcare professionals perceive the severity of threats to their mobile data, they do not feel personally susceptible. Additionally, participants were knowledgeable about security safeguards, but their knowledge of costs and problems related to the adoption of these measures was mixed. These findings indicate that increasing security awareness of healthcare professionals should be a priority.


[Electron microscopic demonstration of pulmonary surfactant proteins using procion brilliant blue H5GS].
A new electron microscopy technique is described for detection of lung surfactant proteins with the copper-containing phthalocyanine dye, procion brilliant blue H5GS. The protein structures were stained concurrently with the fixation during perfusion through the pulmonary artery of a fixative-staining mixture containing glutaric aldehyde and a dye in the kakodilate buffer, pH 5.6-6, and in the course of a subsequent immersion of lung tissue pieces into the same mixture. Then the material was treated with thiosemicarbazide and post-fixed with OsO4. The dye did not penetrate intact cells. The electron-dense products of the histochemical reaction were located inside and on the surface of the surfactant membrane, in the hypophase of the surfactant complex, on the plasmalemma of air-blood barrier cells and in its micropinocytosis vesicles, as well as on the membranes of osmophilic plate-like bodies as their contents egressed into the alveolar lumen.


[The migrant and the Hôpital du Massif Central at the Hôpital Saint-Louis-des-Français in Madrid, 1617-1935].
This article is meant to bring out the interest offered by hospital records for the study of a migratory movement. The example chosen is a medium-distance migration, concerning people leaving the Massif central for Spain. The subject of our observation is the "Hôpital de Saint Louis des Français" in Madrid. It was a small establishment, but one whose exiguity is offset--for the observer--by its longevity (1617-1935). This means thousands of entries and, for the historian, a stock-in-trade which, although deficient at times, sheds a new light on a migratory movement as long-lived as the hospital itself. Over three centuries, we can trace enduring regional and occupational trends as well as departures from those trends, whose statistics can be made. Thus, the standard Auvergnat who never fails to give his patronage to the Hôpital de Saint Louis des Français--more than a third of its inmates until the 19th century--that itinerant provider of small services, can be seen to settle gradually in Madrid, confining himself to the bakery trade. If that occupational evolution can be easily discerned, a more subtle analysis makes it possible to detect the departures from the trends in the parishes from which they emigrated, and to make comparisons with other French migrants. Moreover, better than any other document, the Infirmary Register throws light on the often hidden side of emigration: disease, poverty and failure.


Postcolumn derivatization method for determination of reducing and phosphorylated sugars in chicken by high performance liquid chromatography.
A postcolumn derivatization method is described for determination of reducing sugars and phosphorylated reducing sugars from chicken meat and other foods using high-performance liquid chromatography (HPLC). Reducing sugars are extracted with ethanol/water, separated on a Kromasil amine-bonded column by isocratic analysis using acetonitrile/water as the mobile phase, and, after postcolumn reaction with tetrazolium blue, are determined by the resulting absorbance at 550 nm. Phosphorylated sugars are first dephosphorylated using alkaline phosphatase and then determined by the same method.


The immunopathology of the small intestinal reaction in gluten-sensitivity.
Computerised image-analysis was used to define the spectrum of immunopathological changes in small intestinal mucosa in established celiac sprue disease; dermatitis herpetiformis; 1 degree relatives of celiac sprue patients, and treated celiac sprue patients challenged with varying doses of a peptic-tryptic digest of gluten. Typically, in flat ('Type 2') lesion there was a reduced number of large, mitotically active lymphocytes in surface epithelium, but an increased lymphocyte population in crypts. In approximately 50% untreated DH patients and in 20% 1 degree celiac sprue relatives, mucosal architecture was well-preserved although surface (villous) epithelium contained an expanded population of small, non-mitotic lymphocytes ('Type 1' lesion), with or without crypt hyperplasia. Similar changes were also induced by small dose gluten challenge. Larger dose challenges caused a progression from a Type 1 to a Type 2 lesion during a 5 day period of observation. In addition, observations on a few patients over 2-4 years showed a similar sequence of mucosal changes. A major feature of this sequence was the early appearance of crypt hypertrophy, before significant villous flattening had occurred. These changes parallel T lymphocyte-mediated graft- versus-host reactions in animals, suggesting that the specific immunopathologic features seen in gluten sensitivity are fundamentally cell-mediated in type, the degree of change probably dependent on host genetic factors. Finally, these data show that in becoming flat the mucosa must initially pass through the earlier Type 1 lesion in which crypt hypertrophy is a prominent response.


Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses.
Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which the 3'-terminal part of EWS at 22q is replaced by the 3'-terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases, 7 of which showed the characteristic t(12;22). As an initial step in the characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an exon/intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred, was to a large extent (83%) composed of repetitive elements. RT-PCR amplified EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10 patients. Four types of EWS/ATF1 chimeric transcript, designated types 1-4, were identified. The most frequent chimeric transcript (type 1) was an in-frame fusion of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5 patients but found together with other variants in 3 tumors. The type 2 transcript of EWS/ATF1, an in-frame fusion of exon 7 of EWS with exon 5 of ATF1, was detected in 4 patients, as the only transcript in 1 case and together with other variants in 3 cases. An in-frame fusion of exon 10 of EWS with exon 5 of ATF1 (type 3) was found in 1 patient as the only transcript, and an out-of-frame fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10, resulting in an out-of-frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon 4) was fused with EWS exon 8; at the junction, there was an insertion of 4 nucleotides, also resulting in an out-of-frame transcript. Genomic extra long PCR and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS and intron 3 and exon 4 of ATF1. While a simple end-to-end fusion was observed in 2 cases, additional nucleotides were found at the junctions in 2 other cases. In addition, topoisomerase I consensus sequences were found close to the junctions, suggesting that this enzyme may participate in the genesis of the EWS/ATF1 fusion.


Light-driven hydrogen production from aqueous solutions based on a new Dubois-type nickel catalyst.
In this work, we report a new photocatalytic system that links multifunctional semiconductor nanocrystals with emerging water-soluble molecular catalysts made of earth-abundant elements for H2 generation [Ni(P2RN2R')2(BF4)2]4-, R = Ph, R' = [PhSO3]- (NiS). This noble metal free hybrid exhibits remarkable catalytic activity with a turnover number of 511 for H2 production and a photon-to-H2 conversion efficiency of 12.5%. The mechanistic insight into such high efficiency in this photocatalytic system was examined using a combination of steady-state emission and time-resolved absorption spectroscopy.


Comparison of the levels of copper, zinc and iron in cervical mucus and in blood serum of women of childbearing age.
The objective of this research study was a preliminary comparison of some chosen trace elements concentrations in cervical mucus and blood serum of women of childbearing age. The levels of iron (Fe), copper (Cu) and zinc (Zn) were determined in cervical mucus and serum of 10 patients. The obtained results do not point to any association between the levels of the examined trace elements in cervical mucus or any correlation between their contents in mucus and blood serum. As no correlation was found between the blood serum and cervical mucus, as far as trace elements are concerned, one might suggest that the uptake of trace elements by the mucus has an active form.


Medically Disqualifying Conditions Among Aircrew Candidates.
BACKGROUND: Medical selection criteria for Israeli Air Force (IAF) Flight Academy candidates are strict due to the extreme physiological stressors during military flight. In various air forces the causes for medical disqualification of Flight Academy candidates are different, mainly due to differences in the selection process and criteria. In the present study, we examined the medical conditions leading to disqualification of candidates for the IAF Flight Academy.METHODS: We reviewed the medical records of 3281 military Flight Academy candidates who underwent medical evaluation in the IAF Aeromedical Center between June 2016 and March 2018. For each disqualified candidate, we examined the cause or causes for disqualification divided into categories.RESULTS: Out of 3281 Flight Academy candidates, 519 candidates (15.8%) were disqualified. The most prevalent cause for disqualification were ophthalmological conditions, which constituted more than half of the disqualifications (55.0%). Among the ophthalmological conditions, nonsatisfactory visual acuity constituted more than half (57.4%). The following most prevalent causes were asthma (7.9%), allergic rhinitis (7.3%), renal and urinary conditions, and otolaryngologic conditions (5.2% each).DISCUSSION: The leading cause for disqualification of Flight Academy candidates was ophthalmological conditions, similar to other air forces. Our findings warrant an ongoing review of criteria for disqualification.Groner O, Frenkel-Nir Y, Erlich-Shoham Y, Shoval G, Gordon B. Medically disqualifying conditions among aircrew candidates. Aerosp Med Hum Perform. 2022; 93(4):384-389.


Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells.
The genetic circuits that allow cancer cells to evade immune killing via epithelial mesenchymal plasticity remain poorly understood. Here, we showed that mesenchymal-like (Mes) KPC3 pancreatic cancer cells were more resistant to cytotoxic T lymphocyte (CTL)-mediated killing than the parental epithelial-like (Epi) cells and used parallel genome-wide CRISPR screens to assess the molecular underpinnings of this difference. Core CTL-evasion genes (such as IFN-γ pathway components) were clearly evident in both types. Moreover, we identified and validated multiple Mes-specific regulators of cytotoxicity, such as Egfr and Mfge8. Both genes were significantly higher expressed in Mes cancer cells, and their depletion sensitized Mes cancer cells to CTL-mediated killing. Notably, Mes cancer cells secreted more Mfge8 to inhibit proliferation of CD8+ T cells and production of IFN-γ and TNFα. Clinically, increased Egfr and Mfge8 expression was correlated with a worse prognosis. Thus, Mes cancer cells use Egfr-mediated intrinsic and Mfge8-mediated extrinsic mechanisms to facilitate immune escape from CD8+ T cells.


Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer.
The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. All patients had KRAS wild-type metastatic colorectal cancer and had previously received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well. All patients had progressed within 3 months after the last given treatment before starting the triple combination therapy every second week. Sixty-three patients were evaluated. The triple combination therapy was well tolerated. The median progression-free survival was 6.1 months, and the median overall survival was 11.9 months. Four patients (6%) obtained a partial response, and 40 (63%) had stable disease. The combination of irinotecan, bevacizumab, and cetuximab/panitumumab is safe and shows a toxicity profile corresponding to what is expected from the agents alone. The results indicate that the combination in the 4th line may result in a high rate of disease control in heavily pretreated patients with metastatic colorectal cancer.


Differentiating malignant and benign pleural effusion in patients with lung cancer: an 18F-FDG PET/CT retrospectively study.
To explore the clinical role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung cancer. Over a 8-year period, we retrospectively reviewed PET/CT data of lung cancer patients with pleural effusion, with 237 participants enrolled for analysis. The nature of pleural effusion was confirmed using pleural cytology or biopsy. MPE versus BPE comparison and multiple regression analysis were performed. Receiver operating characteristic (ROC) curve analysis was used for evaluating the diagnostic performance. Of the 237 participants, 170 had MPEs and 67 had BPEs. Compared with BPEs, MPEs had higher pleural SUVmax and thicker pleura and were more common among non-small cell lung cancers, peripheral tumors, and women (p < 0.05). BPEs had larger and higher 18F-FDG uptake thoracic lymph nodes and more complications of pneumonia (p < 0.05) than MPEs. Multiple regression analysis was used to identify the pleural SUVmax (odds ratio, OR = 38.8), sex (OR = 0.033), and mediastinal lymphoid node size (OR = 0.86) as independent risk factors for MPEs. The sensitivity, specificity, and area under the ROC curve (AUC) in the combined ROC curve analysis by using the three factors were 95.3%, 95.5%, and 0.989, respectively. 18F-FDG PET/CT integrated imaging is an effective non-invasive method for differential diagnosis of MPE in patients with lung cancer. Pleural SUVmax combined with thoracic lymph nodes and sex has high diagnostic value.


Survey of Japanese ophthalmic surgeons regarding perioperative disinfection and antibiotic prophylaxis in cataract surgery.
To elucidate Japanese trends for perioperative disinfection and antibiotic selection during cataract surgeries. Perioperative iodine use and antibiotic prophylaxis for cataract surgery were surveyed in eight regions in Japan by mail or through interviews from February 1 to March 1, 2014. We surveyed 572 surgeons, of whom 386 (67%) responded. Most of the surgeons (94%) used iodine compounds before surgery for periocular skin disinfection (povidone-iodine [PI]: 79%; polyvinyl alcohol-iodine [PAI]: 15%) or conjunctival disinfection (85%; PI: 36%; PAI: 49%). Preoperative conjunctival iodine was primarily used as an eye wash (irrigation: 95%) and less often as an eye drop (5%). It was determined that 31% of surgeons waited 30 seconds or more between periocular disinfection and conjunctival disinfection. During surgery, 14% of surgeons used iodine several times, including immediately before intraocular lens insertion, and 7% used the Shimada technique (repeated iodine irrigation). Preoperative antibiotic eye drops were used by 99% of surgeons, and antibiotics were added to the irrigation bottle by 22%. The surgeons reported use of subconjunctival antibiotic injections (23%), antibiotic ointments (79%), and intracameral antibiotics (7%: 22 moxifloxacin; 6 levofloxacin). All surgeons prescribed postoperative eye drops, with 10% initiating the drops on the day of surgery. Iodine compounds are commonly used preoperatively, but few institutions use iodine compounds intraoperatively, particularly with repeated application. The selection of antibiotic administration and disinfection technique has to be at the surgeon's discretion. However, intracameral antibiotic and intraoperative iodine compound use are techniques that should be widely recognized.