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Abstract Background Forkhead transcription factors belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and mammals. In Drosophila, the insulin-signaling pathway regulates the size of cells, organs, and the entire body in response to nutrient availability, by controlling both cell size and cell number. In this study, we present a genetic characterization of dFOXO, the only Drosophila FOXO ortholog. Results Ectopic expression of dFOXO and human FOXO3a induced organ-size reduction and cell death in a manner dependent on phosphoinositide (PI) 3-kinase and nutrient levels. Surprisingly, flies homozygous for dFOXO null alleles are viable and of normal size. They are, however, more sensitive to oxidative stress. Furthermore, dFOXO function is required for growth inhibition associated with reduced insulin signaling. Loss of dFOXO suppresses the reduction in cell number but not the cell-size reduction elicited by mutations in the insulin-signaling pathway. By microarray analysis and subsequent genetic validation, we have identified d4E-BP, which encodes a translation inhibitor, as a relevant dFOXO target gene. Conclusion Our results show that dFOXO is a crucial mediator of insulin signaling in Drosophila, mediating the reduction in cell number in insulin-signaling mutants. We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP.

Background: Preferences and wishes of patients is an important indicator of primary health care provision, although there are differences between national primary care systems., Aim: The aim of this paper is to describe and evaluate the preferences and values of Hungarian primary care (PC) patients before accessing and to analyse their experiences after attending PC services., Methods: In the Hungarian arm of the European QUALICOPC Study, in 2013-2014, information was collected with questionnaires; the Patient Values contained 19 and the Patient Experiences had 41 multiple-choice questions., Findings: The questionnaires were filled by 2149 (840 men, 1309 women) using PC services, aged 49.1 (SD ± 16.7) years, 73% of them having chronic morbidities. Women preferred to be accompanied and rated their own health better. Patients in the lowest educational category and women visited their GPs more often, and they are consulted more frequently by other doctors as well. Men, older and secondary educated people reported more frequently chronic morbidities. Longer opening hours were preferred by patients with higher education. The most preferred expectations were availability and polite communication of doctors, not pressures on consultation time, clear instructions provided during consultations, shared decisions about treatments and options for consultations, the knowledge of the doctors concerning the living conditions, social and cultural backgrounds of patients, updated medical records, short waiting times, options for home visits, wide scope of professional competences and trust in the doctor., Conclusion: Wishes, preferences of patients and fulfilment were similar than described in other participating countries of the study. Although there are room to improve PC services, most of the questioned population were satisfied with the provision.

Sulpha drugs are widely employed in medicine for various diseases and disorders. During the last several decades, numerous papers had been published on supra ciliary and posterior choroidal effusion likely presenting as an idiosyncratic effect of these drugs especially of acetazolamide. In each publication, the effusion was associated with either an acute angle-closure glaucoma or transitory myopia or both of these as leading symptoms. In the current publication, authors report on two cases where the acetazolamide-induced choroidal effusion was an accidental finding without either a myopic shift in refraction or an acute elevation in intraocular pressure. To our best knowledge, ours is the first report in the literature describing this unusual, "silent" form of a sulpha drug-induced choroidal effusion. Since the choroidal involvement may vary in size and location, and is not necessarily associated with acute glaucoma and myopia, one can assume that a considerable amount of acetazolamide-related ocular side-effects will not be discovered. The above case report aims to draw the attention of other specialities to the need for ophthalmic examination for their patients taking sulpha drugs with acute visual deterioration. Orv Hetil. 2017; 158(50): 1998-2002.

Measles, caused by the Morbilli virus, is a highly (about 95 %) contagious disease affecting primarily children, but without proper immunisation, adults can also be infected. The leading symptoms of the disease are high fever that presents after an incubation period of 9-10 days and the red rash that begins several days after the fever starts. Beyond specific generalized symptoms, measles may have ocular symptoms. The most commonly occurring conjunctivitis, the so-called "red eye symptom", is not characteristic only for measles infection, however, by taking the generalized symptoms it can suggest the diagnosis at the beginning of the disease. Conjunctivitis of varying severity is noticed in the half of the cases without using ophthalmological instrumentation. Using ophthalmological instrumentation, the mild forms of conjunctivitis can be diagnosed, by meticulous ophthalmological examination, further eye diseases can be discovered. The viral conjunctivitis can progress to keratitis and bacterial superinfection can occur. If the infection presents in childhood it can affect the posterior segment. The fight against measles is very effective in Hungary since the vaccination has been introduced, and the lack of vaccination is also the primary cause of the risk to the disease. In the diagnosis, symptomatic treatment of the disease and the curbing of possible mass infections, the practicing physician (general practitioner) has a key role. The correct care of the infected patient in Hungary is provided by a methodological letter, professional information and legal guides. Orv Hetil. 2017; 158(39): 1523-1527.

Ocular signs and symptoms of Ebola infection initially suggest banal conjunctivitis, but in advanced cases severe haemorrhagic conjunctivitis appears and, in the final stage of the disease, retinal and chorioidal haemorrhages may occur which can cause even blindness. Although the viral infection accompanied by ocular symptoms of a non-specific conjunctivitis, the high fever present from the onset of the disease should raise the suspicion of Ebola infection. There is no causal therapy know so far, and the only adjunctive treatment may be delivered by an ophthalmologist. Because the virus can be detected in the tear, it can theoretically be the mediator of the infection and, therefore, ophthalmological examinations should be carried out with the highest caution. In case of suspected Ebola infection the nearest competent healthcare authority should be immediately alerted in order to take further actions.

Introduction: Besides medical treatment, adequate communication and personal relationships between physicians and patients are the most important determinants of patient satisfaction., Aim: To explore doctor-patient relationships, and factors that may determine patient satisfaction with care., Method: Patients with gastroesophageal reflux (n = 80) were divided into subgroups treated by family doctors or by gastroenterologists. Patients were asked to fill in a questionnaire about communication and patient satisfaction., Results: Significantly more patients visited family doctors than gastroenterologists with health problems (80%; 20%, p < 0.001). Patients were significantly more satisfied with the information they received about the process of care provided by family doctors (95%) compared to that they obtained from gastroenterologists (65%; p = 0.002). Significantly more patients in family practices indicated that their doctors spent enough time with them compared to subspecialists (96.7%; 80% p = 0.032)., Conclusions: Patients develop a closer personal relationship and more appropriate communication with family doctors compared to specialists, which can be an important component of successful treatment.

Background: Ingestion of sulphonamide-derived drugs has been reported to possibly have ocular side-effects. Authors aimed to present a rare case of indapamide-induced transient myopia with ciliary body edema and supraciliary effusion., Case Presentation: A 39 years old caucasian female patient presented at the Department of Neurology with headache and sudden bilateral loss of distant vision. Neurological assessment and cranial CT scans were unremarkable. For her hypertension, twice a day bisoprolol 2.5 mg and once a day indapamide 1.5 mg tablets were prescribed several days before. At her presenting, ophthalmic findings were as follows: visual acuity 0.08-7.25Dsph = 1.0 and 0.06-7.25Dsph = 1.0; IOP 25 mmHg and 24 mmHg, anterior chamber depth (ACD) 2.32 mm and 2.49 mm, lens thickness (L) 4.02 mm and 4.09 mm in the right and the left eye, respectively. By means of ultrasound biomicroscopy (UBM), thickened (720 / 700 micron) and detached ciliary body, its forward movement (ciliary body-cornea angle 108' / 114') and forward rotated ciliary processes were seen. Angle opening distance (AOD500) were 300 / 314 microns. By the following days, the myopia gradually diminished, and a week after her first symptoms, her uncorrected visual acuity was 1.0 in both eyes, IOP 13 mmHg and 17 mmHg, ACD 3.68 mm and 3.66 mm, L 3.78 mm and 3.81 mm in the right and the left eye, respectively. Ciliary body edema and detachment disappeared (ciliary body thickness 225 / 230 micron), both of the ciliary body-cornea angle 134' / 140' and the AOD500 (650 / 640 microns) increased. At this point, the patient admitted that she had stopped taking indapamide two days before., Conclusions: Our case report is the third one in the literature to present indapamide-induced transient myopia, and the first to employ UBM for describing the characteristics of this rare condition. According to the findings, authors suggest that both ciliary muscle contraction and ciliary body edema may play role in the pathomechanism. UBM seems to be a useful tool in the differential diagnosis of acute myopia. Further, authors wish to draw attention to one of the potential adverse effects of this drug which was not listed by its package insert.

The importance of primary care has already been recognized in the developed countries, where the structure and function of primary care is very heterogeneous. In the QUALICOPC study, the costs, quality and equity of primary care systems will be compared in the 34 participating countries. Representative samples of primary care practices were recruited in Hungary. An evaluation with questionnaire was performed in 222 practices on the work circumstances, conditions, competency and financial initiatives. Ten patients in each practice were also questioned by independent fieldworkers. In this work, the methodology and Hungarian experience are described. The final results of the international evaluation will be analyzed and published later. It is expected that data obtained from the QUALICOPC study may prove to be useful in health service planning and may be shared with policy makers.

Unlabelled: Hospitalization attributable to gastrointestinal and other major bleeding is frequently associated with acenocoumarol treatment., Aims: To assess the level of knowledge among patients in respect to harmful adverse effects, interactions with medication and nutrition regarding acenocoumarol treatment., Methods: Questionnaires consisting of 66 questions were completed in offices of family doctors (77), and during consultations at the 3rd Department of Internal Medicine (80)., Results: 157 patients (male:female=45:55; age=65.5 years) were involved. In the group informed by the whole team (doctors, nurses and dietitians) everyone heard about the possible adverse effects. In the group where family doctors or other specialists provided information, 14.5% or 31.1% did not hear about any side-effect. The importance of diet was unknown by 71.4% of the patients. The knowledge of interactions between acenocoumarol and other medications is low: aspirin was known by 24.4%, analgetics by 23.0% and vitamin K by 18.6% of the patient., Conclusions: Regarding acenocoumarol treatment, patients' knowledge should be enlarged. However, it can be significantly improved by the contribution of other team members such as nurses and dietitians.

Erdheim-Chester's disease is a rare multisystem xanthogranulomatosis, afflicting the skeletal system with the occasional involvement of soft tissues. We delineate an unusual case of a cardiac variant of Erdheim-Chester's disease presenting with pericardial effusion and as a collision with a synchronous orbital manifestation. We describe our diagnostic pathway and propose a novel treatment option involving nonsteroidal anti-inflammatory drugs. The role of cyclo-oxygenase in the disease process and inhibition thereof by NSAIDs is hypothesized and discussed.

The development of multicellular organisms requires the establishment of cell populations with different adhesion properties. In Drosophila, a cell-segregation mechanism underlies the maintenance of the anterior (A) and posterior (P) compartments of the wing imaginal disc. Although engrailed (en) activity contributes to the specification of the differential cell affinity between A and P cells, recent evidence suggests that cell sorting depends largely on the transduction of the Hh signal in A cells. The activator form of Cubitus interruptus (Ci), a transcription factor mediating Hh signaling, defines anterior specificity, indicating that Hh-dependent cell sorting requires Hh target gene expression. However, the identity of the gene(s) contributing to distinct A and P cell affinities is unknown. Here, we report a genetic screen based on the FRT/FLP system to search for genes involved in the correct establishment of the anteroposterior compartment boundary. By using double FRT chromosomes in combination with a wing-specific FLP source we screened 250,000 mutagenized chromosomes. Several complementation groups affecting wing patterning have been isolated, including new alleles of most known Hh-signaling components. Among these, we identified a class of patched (ptc) alleles exhibiting a novel phenotype. These results demonstrate the value of our setup in the identification of genes involved in distinct wing-patterning processes.

Background: Forkhead transcription factors belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and mammals. In Drosophila, the insulin-signaling pathway regulates the size of cells, organs, and the entire body in response to nutrient availability, by controlling both cell size and cell number. In this study, we present a genetic characterization of dFOXO, the only Drosophila FOXO ortholog., Results: Ectopic expression of dFOXO and human FOXO3a induced organ-size reduction and cell death in a manner dependent on phosphoinositide (PI) 3-kinase and nutrient levels. Surprisingly, flies homozygous for dFOXO null alleles are viable and of normal size. They are, however, more sensitive to oxidative stress. Furthermore, dFOXO function is required for growth inhibition associated with reduced insulin signaling. Loss of dFOXO suppresses the reduction in cell number but not the cell-size reduction elicited by mutations in the insulin-signaling pathway. By microarray analysis and subsequent genetic validation, we have identified d4E-BP, which encodes a translation inhibitor, as a relevant dFOXO target gene., Conclusion: Our results show that dFOXO is a crucial mediator of insulin signaling in Drosophila, mediating the reduction in cell number in insulin-signaling mutants. We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP.

Generally, toxoplasmosis has mild symptoms, or is asymptomatic, in patients with intact immune system. The infection, however, may have serious consequences in immunodeficient or immunosuppressed patients, as well as in the off-springs of pregnant women. If the mother has acute toxoplasmosis during the pregnancy, the passage of parasites through the placenta may result in the death of the fetus, or, in the severe damage of the fetus or neonate. All these consequences can be prevented by the early detection of the disease followed by the immediate therapy of the mother. Contrary to the most infectious diseases, however, the high specific IgM level has not proved to be a reliable marker of the acute infection in the case of toxoplasmosis. Therefore, in the case of infections discovered in the "plateau" period [i.e. with persistent IgM ("residual" IgM) and/or persistent high level of IgG antibody), the "acute" and the "chronic" phases can be distinguished more reliably by the detection with ELISA of the IgA antibody response to the so called P30 protein of Toxoplasma gondii. The anti-P30 IgA antibody response appears very early and generally disappears in 3-9 months. Thus, it is possible to discriminate the acute phase of the disease from the harmless chronic phase. Between 1987 and 1996, practically all pregnant women in Szeged and its region (altogether 21,952 women), underwent serologic toxoplasma screening. Among them, 124 pregnant women were found highly suspicious for having acute toxoplasmosis. Appropriate counselling, followed by spiramycin therapy during pregnancy and regular ultrasound examination were their antenatal management. No clinically manifested fetal or neonatal infection was observed. The screening and treatment schedule seems to be promising in the prevention of fetal and neonatal toxoplasmosis.

Energy charge controls intermediary metabolism and cellular regulation. Here we show that inhibition of energy conservation at the level of glucose uptake, glycolysis, citric acid cycle, and oxidative phosphorylation induces cell death, leading to fragmentation of DNA into an oligonucleosomal ladder and morphological changes typical for apoptosis. Bcl-2, the prototype of oncogenes that suppress cell death, efficiently inhibits apoptosis induced by metabolic inhibitors. Bcl-2 does not antagonize the inhibitory potential of mitochondrial inhibitors, and cannot prevent or delay the decrease of the cellular ATP level subsequent to metabolic inhibition. Thus, we propose that Bcl-2 blocks apoptosis at a point downstream of the collapse of the cellular-energy homeostasis.

Ophthalmic examinations were performed for determining the suitability of seven different types of non-ophthalmic ultrasound equipments for ophthalmological purposes. According to the results, the instruments with probes of 5 MHz or higher frequency are appropriate for certain screening ophthalmological purposes in hospitals where ophthalmic ultrasound instrument is still missing. The possible indications are: approximate estimation of axial eye length for intraocular lens calculation, and visualization of gross intraocular and orbital diseases, such as retinal detachment, tumours, foreign bodies etc. In case of pathological result or in case of axial eye length different from the average value, the high resolution ophthalmological ultrasound examination is mandatory. The modern colour-coded Doppler ultrasound equipments were found suitable for the examination of the circulation of the eye and orbit.

Recurrent corneal erosion can develop after superficial trauma and can prove unresponsive to traditional forms of conservative treatment. Over the past 5 years, we have treated 17 unilateral cases with our own surgical technique. The following method was applied for treatment: under an operating microscope the separated corneal epithelium was excised with microforceps and Vannas microscissors. After this, the underlying hypertrophic basement membrane was peeled off Bowman's membrane with a foreign body needle and excised at the rim with Vannas microscissors. The site of hyalin-like formation adhering on the area of Bowman's membrane was next carefully scraped with the foreign body needle. Following this procedure, a dressing lens was fitted to the eye. In 2 cases recurrences occurred, but the healing process was successful in these cases after treatment. With this simplified microsurgical procedure, the recurrent corneal erosion was curable. Through the application of dressing lenses, the danger of recurrence was eliminated, and the healing process was considerably shortened.

A case of an 8-year-old girl with unilateral retinoblastoma is presented. The clinical picture was dominated by inflammatory signs and retinal detachment. Ultrasonographic A/B-scan showed a funnel-shaped total retinal detachment and a thick solid mass with similar shape just behind it. The main characteristics of the mass were: irregular inside echo pattern, medium high internal reflectivity, no sign of vascularity, no after movements following a sudden ocular movement, and no shadowing of the scleral or orbital tissues behind it. The vitreous cavity in front of the retina and behind the mass was ultrasonographically clear. The described funnel-shaped echographic pattern might be typical of the diffuse infiltrating retinoblastoma.

Ultrasonographic examinations of the lacrimal drainage system demonstrated that the Ultrascan System IV apparatus used was not able to represent the normal-size lacrimal canaliculi, the common canaliculus, the lower part of the nasolacrimal duct and the lacrimal ostium. It can be used routinely, however, in the diagnostics of diseases of the lacrimal sac and its surrounding tissue, for surgical indication and in order to examine the postoperative condition, in most cases without other expensive diagnostic methods. The advantages over dacryocystography are that it is simple, quick, and inexpensive, it can be used post-operatively immediately, the patient is not exposed to radiation, it can be used without any contrast medium, and it is useful when the common canaliculus is occluded.

A- und B-scan echography is a useful method for the examination of certain parts of the lacrimal drainage system. In most cases it can substitute for dacryocystography and other expensive methods in the diagnosis of lacrimal sac diseases. Older methods of echography for examination of the lacrimal sac are direct contact, water bath, and rarely transocular contact methods. We have developed a new method, in which a rubber tube filled with fluid is placed between the transducer and the skin surface. Comparison of these methods demonstrates that this is the best method for ultrasound diagnostics of the lacrimal sac because it can be carried out as easily as the direct contact method, and the quality of the echograms is as good as in the water bath method. A special advantage is that causing an infection in the patient with the ultrasound probe can be avoided.

An NADPH-driven enzymatic reduction of an Fe(III)ADP complex by rat liver microsomes has been demonstrated directly for the first time during the initial phase of lipid peroxidation by using two different analytical methods. The reduction rate increased upon increasing the ratio of ADP to ferric iron. Fe(III)ADP reducing activity of both detergent-solubilized microsomes and purified NADPH:cytochrome-P-450 (cytochrome-c) reductase decreased to about 20% compared to that of the native microsomes. Superoxide dismutase and KCN did not inhibit the reduction.

Heme-nonapeptide, derived from cytochrome c, inhibited both the NADPH- and NADH-dependent lipid peroxidation of brain microsomes but, in the case of liver microsomes, this inhibitory effect manifested itself in the presence of SKF-525A (a specific blocker of cytochrome P-450) only. Heme-nonapeptide prevented the transient accumulation of lipid peroxides in microsomes during lipid peroxidation. The oxygen consumption of microsomes in the presence of NADPH or NADH was stimulated by heme-nonapeptide. From these results we concluded that, in vitro, there are two independent mechanisms of lipid peroxidation in liver microsomes. It is suggested that, in vivo, the heme-peptide-sensitive mechanism, observed in brain microsomes, is more important.

The interaction of heme nonapeptide (a proteolytic product of cytochrome c) with purified NADH:cytochrome b5 (EC 1.6.2.2) and NADPH:cytochrome P-450 (EC 1.6.2.4) reductases was investigated. In the presence of heme nonapeptide, NADH or NADPH were enzymatically oxidized to NAD+ and NADP+, respectively. NAD(P)H consumption was coupled to oxygen uptake in both enzyme reactions. In the presence of carbon monoxide the spectrum of a carboxyheme complex was observed during NAD(P)H oxidation, indicating the existence of a transient ferroheme peptide. NAD(P)H oxidation could be partially inhibited by cyanide, superoxide dismutase and catalase. Superoxide and peroxide ions (generated by enzymic xanthine oxidation) only oxidized NAD(P)H in the presence of heme nonapeptide. Oxidation of NAD(P)H was more rapid with O2- than O2-2. We suggest that a ferroheme-O2 and various heme-oxy radical complexes (mainly ferroheme-O-2 complex) play a crucial role in NAD(P)H oxidation.

Heme-nonapeptide inhibits NADH and NADPH dependent lipid peroxidation of brain microsomes in the presence or absence of ADP-Fe complex. The transient accumulation of lipid peroxides during NADH or NADPH dependent, ADP-Fe stimulated lipid peroxidation, is inhibited by heme-nonapeptide. Oxygen consumption of brain microsomes in the presence of NADH or NADPH is stimulated by heme-nonapeptide. Reduction of cytochrome-c and nitro-tetrazolium-blue by O2- generated by xanthine oxidase is inhibited by heme-nonapeptide.

The disease process of uveitis due to Toxocara canis infection has a much more severe course in children than in adults. It can be cured by special drugs (Mintezol) and corticosteroids, which at the same time also reduce the inflammatory symptoms. In patients with endophthalmitis, vitrectomy may be indicated. The improvement in visual acuity depends both on the localization of the degenerations and on the duration of the disease. The authors consider sonographic examination indispensable for differential diagnosis.