On hierarchical competition through reduction of individual growth.

We consider a population organised hierarchically with respect to size in such a way that the growth rate of each individual depends only on the presence of larger individuals. As a concrete example one might think of a forest, in which the incidence of light on a tree (and hence how fast it grows) is affected by shading by taller trees. The classic formulation of a model for such a size-structured population employs a first order quasi-linear partial differential equation equipped with a non-local boundary condition. However, the model can also be formulated as a delay equation, more specifically a scalar renewal equation, for the population birth rate. After discussing the well-posedness of the delay formulation, we analyse how many stationary birth rates the equation can have in terms of the functional parameters of the model. In particular we show that, under reasonable and rather general assumptions, only one stationary birth rate can exist besides the trivial one (associated to the state in which there are no individuals and the population birth rate is zero). We give conditions for this non-trivial stationary birth rate to exist and analyse its stability using the principle of linearised stability for delay equations. Finally, we relate the results to the alternative, partial differential equation formulation of the model.

Downregulation of PACAP and the PAC1 Receptor in the Basal Ganglia, Substantia Nigra and Centrally Projecting Edinger-Westphal Nucleus in the Rotenone model of Parkinson's Disease.

Numerous in vitro and in vivo models of Parkinson's disease (PD) demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP) conveys its strong neuroprotective actions mainly via its specific PAC1 receptor (PAC1R) in models of PD. We recently described the decrease in PAC1R protein content in the basal ganglia of macaques in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD that was partially reversed by levodopa therapy. In this work, we tested whether these observations occur also in the rotenone model of PD in the rat. The rotarod test revealed motor skill deterioration upon rotenone administration, which was reversed by benserazide/levodopa (B/L) treatment. The sucrose preference test suggested increased depression level while the open field test showed increased anxiety in rats rendered parkinsonian, regardless of the received B/L therapy. Reduced dopaminergic cell count in the substantia nigra pars compacta (SNpc) diminished the dopaminergic fiber density in the caudate-putamen (CPu) and decreased the peptidergic cell count in the centrally projecting Edinger-Westphal nucleus (EWcp), supporting the efficacy of rotenone treatment. RNAscope in situ hybridization revealed decreased PACAP mRNA (Adcyap1) and PAC1R mRNA (Adcyap1r1) expression in the CPu, globus pallidus, dopaminergic SNpc and peptidergic EWcp of rotenone-treated rats, but no remarkable downregulation occurred in the insular cortex. In the entopeduncular nucleus, only the Adcyap1r1 mRNA was downregulated in parkinsonian animals. B/L therapy attenuated the downregulation of Adcyap1 in the CPu only. Our current results further support the evolutionarily conserved role of the PACAP/PAC1R system in neuroprotection and its recruitment in the development/progression of neurodegenerative states such as PD.

Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson's disease in the rat.

BACKGROUND: The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson's disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger-Westphal nucleus in human Parkinson's disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat. METHODS: Systemic chronic rotenone administration as well as targeted leptin-saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional-morphological changes. Two-sample Student's t test, Spearman's rank correlation analysis and Mann-Whitney U tests were used for statistics. RESULTS: In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms. CONCLUSIONS: Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson's disease in the rat.

Peptidergic neurons of the Edinger-Westphal nucleus express TRPA1 ion channel that is downregulated both upon chronic variable mild stress in male mice and in humans who died by suicide.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1), a cation channel, is expressed predominantly in primary sensory neurons, but its central distribution and role in mood control are not well understood. We investigated whether TRPA1 is expressed in the urocortin 1 (UCN1)-immunoreactive centrally projecting Edinger-Westphal nucleus (EWcp), and we hypothesized that chronic variable mild stress (CVMS) would reduce its expression in mice. We anticipated that TRPA1 mRNA would be present in the human EWcp, and that it would be downregulated in people who died by suicide. METHODS: We exposed Trpa1 knockout and wild-type mice to CVMS or no-stress control conditions. We then performed behavioural tests for depression and anxiety, and we evaluated physical and endocrinological parameters of stress. We assessed EWcp Trpa1 and Ucn1 mRNA expression, as well as UCN1 peptide content, using RNA-scope in situ hybridization and immunofluorescence. We tested human EWcp samples for TRPA1 using reverse transcription polymerase chain reaction. RESULTS: Trpa1 mRNA was colocalized with EWcp/UCN1 neurons. Non-stressed Trpa1 knockout mice expressed higher levels of Ucn1 mRNA, had less body weight gain and showed greater immobility in the forced swim test than wild-type mice. CVMS downregulated EWcp/Trpa1 expression and increased immobility in the forced swim test only in wild-type mice. We confirmed that TRPA1 mRNA expression was downregulated in the human EWcp in people who died by suicide. LIMITATIONS: Developmental compensations and the global lack of TRPA1 may have influenced our findings. Because experimental data came from male brains only, we have no evidence for whether findings would be similar in female brains. Because a TRPA1-specific antibody is lacking, we have provided mRNA data only. Limited access to high-quality human tissues restricted sample size. CONCLUSION: TRPA1 in EWcp/UCN1 neurons might contribute to the regulation of depression-like behaviour and stress adaptation response in mice. In humans, TRPA1 might contribute to mood control via EWcp/UCN1 neurons.

Epigenetic and Neuronal Activity Markers Suggest the Recruitment of the Prefrontal Cortex and Hippocampus in the Three-Hit Model of Depression in Male PACAP Heterozygous Mice.

Depression and its increasing prevalence challenge patients, the healthcare system, and the economy. We recently created a mouse model based on the three-hit concept of depression. As genetic predisposition (first hit), we applied pituitary adenylate cyclase-activating polypeptide heterozygous mice on CD1 background. Maternal deprivation modeled the epigenetic factor (second hit), and the chronic variable mild stress was the environmental factor (third hit). Fluoxetine treatment was applied to test the predictive validity of our model. We aimed to examine the dynamics of the epigenetic marker acetyl-lysine 9 H3 histone (H3K9ac) and the neuronal activity marker FOSB in the prefrontal cortex (PFC) and hippocampus. Fluoxetine decreased H3K9ac in PFC in non-deprived animals, but a history of maternal deprivation abolished the effect of stress and SSRI treatment on H3K9ac immunoreactivity. In the hippocampus, stress decreased, while SSRI increased H3K9ac immunosignal, unlike in the deprived mice, where the opposite effect was detected. FOSB in stress was stimulated by fluoxetine in the PFC, while it was inhibited in the hippocampus. The FOSB immunoreactivity was almost completely abolished in the hippocampus of the deprived mice. This study showed that FOSB and H3K9ac were modulated in a territory-specific manner by early life adversities and later life stress interacting with the effect of fluoxetine therapy supporting the reliability of our model.

Modelling evolution of virulence in populations with a distributed parasite load.

Modelling evolution of virulence in host-parasite systems is an actively developing area of research with ever-growing literature. However, most of the existing studies overlook the fact that individuals within an infected population may have a variable infection load, i.e. infected populations are naturally structured with respect to the parasite burden. Empirical data suggests that the mortality and infectiousness of individuals can strongly depend on their infection load; moreover, the shape of distribution of infection load may vary on ecological and evolutionary time scales. Here we show that distributed infection load may have important consequences for the eventual evolution of virulence as compared to a similar model without structuring. Mathematically, we consider an SI model, where the dynamics of the infected subpopulation is described by a von Förster-type equation, in which the infection load plays the role of age. We implement the adaptive dynamics framework to predict evolutionary outcomes in this model. We demonstrate that for simple trade-off functions between virulence, disease transmission and parasite growth rates, multiple evolutionary attractors are possible. Interestingly, unlike in the case of unstructured models, achieving an evolutionary stable strategy becomes possible even for a variation of a single ecological parameter (the parasite growth rate) and keeping the other parameters constant. We conclude that evolution in disease-structured populations is strongly mediated by alterations in the overall shape of the parasite load distribution.

Modelling Wolbachia infection in a sex-structured mosquito population carrying West Nile virus.

Wolbachia is possibly the most studied reproductive parasite of arthropod species. It appears to be a promising candidate for biocontrol of some mosquito borne diseases. We begin by developing a sex-structured model for a Wolbachia infected mosquito population. Our model incorporates the key effects of Wolbachia infection including cytoplasmic incompatibility and male killing. We also allow the possibility of reduced reproductive output, incomplete maternal transmission, and different mortality rates for uninfected/infected male/female individuals. We study the existence and local stability of equilibria, including the biologically relevant and interesting boundary equilibria. For some biologically relevant parameter regimes there may be multiple coexistence steady states including, very importantly, a coexistence steady state in which Wolbachia infected individuals dominate. We also extend the model to incorporate West Nile virus (WNv) dynamics, using an SEI modelling approach. Recent evidence suggests that a particular strain of Wolbachia infection significantly reduces WNv replication in Aedes aegypti. We model this via increased time spent in the WNv-exposed compartment for Wolbachia infected female mosquitoes. A basic reproduction number [Formula: see text] is computed for the WNv infection. Our results suggest that, if the mosquito population consists mainly of Wolbachia infected individuals, WNv eradication is likely if WNv replication in Wolbachia infected individuals is sufficiently reduced.

Comparison of VividTrac®, Airtraq®, King Vision®, Macintosh Laryngoscope and a Custom-Made Videolaryngoscope for difficult and normal airways in mannequins by novices.

BACKGROUND: Direct laryngoscopy remains the gold standard for endotracheal intubation and is preferred by experienced operators. However, an increasing number of reports currently support videolaryngoscopy, particularly for novice users. The widespread use of videolaryngoscopy may be limited due to financial limitations, especially in low-income countries. Therefore, affordable single-use scopes are now becoming increasingly popular. We sought to compare these new scopes with direct laryngoscopes and the previously tested videolaryngoscopes in mannequins by novices. METHODS: Fifty medical students were recruited to serve as novice users. Following brief, standardized training, students were asked to execute endotracheal intubation with each of the devices, including the Airtraq®, a custom-made videolaryngoscope, the King Vision®, the Macintosh laryngoscope and the VividTrac®, on an airway trainer (Laerdal Airway Management Trainer®) in normal and difficult airway scenarios. We evaluated the time to and the proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma and user satisfaction. RESULTS: We observed no differences in esophageal intubation. However, intubation-related times, the view of the glottis and operator satisfaction were significantly better throughout the study with the commercial videolaryngoscopes. In comparison, the custom-made videolaryngoscope performance proved to be similar to that of the Macintosh laryngoscope. The VividTrac® performance was similar (P > 0.05) or significantly better than that of the King Vision® in both scenarios. CONCLUSIONS: Based upon our results, the Airtraq®, King Vision® and VividTrac® were superior to the Macintosh laryngscope in both normal and difficult airway scencarios for novice users. In particular, our study is the first to report that the VividTrac® shows promise for further clinical evaluation.

Effects of Postnatal Enriched Environment in a Model of Parkinson's Disease in Adult Rats.

Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson's disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

Comparison of Macintosh Laryngoscope, King Vision®, VividTrac®, AirAngel Blade®, and a Custom-Made 3D-Printed Video Laryngoscope for Difficult and Normal Airways in Mannequins by Novices-A Non-Inferiority Trial.

Background: Endotracheal intubation (ETI) is a cornerstone of airway management. The gold standard device for ETI is still the direct laryngoscope (DL). However, video laryngoscopes (VLs) are now also widely available and have several proven advantages. The VL technique has been included in the major airway management guidelines. During the COVID-19 pandemic, supply chain disruption has raised demand for 3D-printed medical equipment, including 3D-printed VLs. However, studies on performance are only sparsely available; thus, we aimed to compare 3D-printed VLs to the DL and other VLs made with conventional manufacturing technology. Methods: Forty-eight medical students were recruited to serve as novice users. Following brief, standardized training, students executed ETI with the DL, the King Vision® (KV), the VividTrac® (VT), the AirAngel Blade® (AAB), and a custom-made 3D-printed VL (3DVL) on the Laerdal® airway management trainer in normal and difficult airway scenarios. We evaluated the time to and proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma, and user satisfaction. Results: The KV and VT are proved to be superior (p < 0.05) to the DL in both scenarios. The 3DVL's performance was similar (p > 0.05) or significantly better than that of the DL and mainly non-inferior (p > 0.05) compared to the KV and VT in both scenarios. Regardless of the scenario, the AAB proved to be inferior (p < 0.05) even to the DL in the majority of the variables. The differences between the devices were more pronounced in the difficult airway scenario. The user satisfaction scores were in concordance with the aforementioned performance of the scopes. Conclusions: Based upon our results, we cannot recommend the AAB over the DL, KV, or VT. However, as the 3DVL showed, 3D printing indeed can provide useful or even superior VLs, but prior to clinical use, meticulous evaluation might be recommended.

Expression and distribution of pituitary adenylate cyclase-activating polypeptide receptor in reactive astrocytes induced by global brain ischemia in mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neuroprotectant. We previously showed that PACAP receptor (PAC1R) immunoreactivity was elevated in reactive astrocytes after stab wound injury. However, the pattern of PAC1R expression in astrocytes after brain injury is still unknown. In this study, PAC1R expression was evaluated in mouse hippocampal astrocytes after bilateral common carotid artery occlusion. PAC1R mRNA levels in the hippocampus peaked on day 7, and glial fibrillary acidic protein (GFAP) mRNA levels increased from day 3 to day 7 after ischemia. We then observed co-localization of PAC1R and GFAP by double immunostaining. GFAP-immunopositive cells showed signs of hypertrophy 3 days after the ischemia, and by day 7 had fine processes, were hypertrophied, and are known as reactive astrocytes. A low number of PAC1R-immunopositive astrocytes were detectable in the hippocampal area until 3 days after ischemia. PAC1R-positive astrocytes were widely distributed in the hippocampus between day 7 and day 14 after ischemia, and they were converging around the damaged CA1 pyramidal cell layer by day 28. These results suggest that PAC1R might be expressed in the middle to late stage of reactive astrocytes and PACAP plays an important role in the reactive astrocytes after brain injury.

Exposure to enriched environment decreases neurobehavioral deficits induced by neonatal glutamate toxicity.

Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG) is a commonly used taste enhancer causing excitotoxic effects when given in newborn animals. We have previously demonstrated that MSG leads to a delay in neurobehavioral development, as shown by the delayed appearance of neurological reflexes and maturation of motor coordination. In the present study we aimed at investigating whether environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal MSG treatment. Newborn pups were treated with MSG subcutaneously on postnatal days 1, 5 and 9. For environmental enrichment, we placed rats in larger cages, supplemented with different toys that were altered daily. Normal control and enriched control rats received saline treatment only. Physical parameters such as weight, day of eye opening, incisor eruption and ear unfolding were recorded. Animals were observed for appearance of reflexes such as negative geotaxis, righting reflexes, fore- and hindlimb grasp, fore- and hindlimb placing, sensory reflexes and gait. In cases of negative geotaxis, surface righting and gait, the time to perform the reflex was also recorded daily. For examining motor coordination, we performed grid walking, footfault, rope suspension, rota-rod, inclined board and walk initiation tests. We found that enriched environment alone did not lead to marked alterations in the course of development. On the other hand, MSG treatment caused a slight delay in reflex development and a pronounced delay in weight gain and motor coordination maturation. This delay in most signs and tests could be reversed by enriched environment: MSG-treated pups kept under enriched conditions showed no weight retardation, no reflex delay in some signs and performed better in most coordination tests. These results show that environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal excitotoxicity.

Gender-dependent effects of enriched environment and social isolation in ischemic retinal lesion in adult rats.

Exposure to an enriched environment has been shown to have many positive effects on brain structure and function. Numerous studies have proven that enriched environment can reduce the lesion induced by toxic and traumatic injuries. Impoverished environment, on the other hand, can have deleterious effects on the outcome of neuronal injuries. We have previously shown that enriched conditions have protective effects in retinal injury in newborn rats. It is well-known that the efficacy of neuroprotective strategies can depend on age and gender. The aim of the present study, therefore, was to examine the effects of environmental enrichment and social isolation in retinal ischemia. We used bilateral common carotid artery occlusion to induce retinal hypoperfusion in adult Wistar rats of both genders. Groups were housed in standard, enriched or impoverished conditions. Impoverished environment was induced by social isolation. Retinas were processed for histological analysis after two weeks of survival. In the present study, we show that (1) enriched environment has protective effects in adult ischemic retinal lesion, while (2) impoverished environment further increases the degree of ischemic injury, and (3) that these environmental effects are gender-dependent: females are less responsive to the positive effects of environmental enrichment and more vulnerable to retinal ischemia in social isolation. In summary, our present study shows that the effects of both positive and negative environmental stimuli are gender-dependent in ischemic retinal lesions.

Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy.

According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion. Fluoxetine treatment was applied in chronic variable mild stress (CVMS)-exposed (environmental hit) CD1 mice carrying one mutated allele of pituitary adenylate cyclase-activating polypeptide gene (genetic hit) that were previously exposed to maternal deprivation (epigenetic hit) vs. controls. Fluoxetine reduced the anxiety level in CVMS-exposed mice in marble burying test, and decreased the depression level in tail suspension test if mice were not deprived maternally. History of maternal deprivation caused fundamental functional-morphological changes in response to CVMS and fluoxetine treatment in the corticotropin-releasing hormone-producing cells of the bed nucleus of the stria terminalis and central amygdala, in tyrosine-hydroxylase content of ventral tegmental area, in urocortin 1-expressing cells of the centrally projecting Edinger-Westphal nucleus, and serotonergic cells of the dorsal raphe nucleus. The epigenetic background of alterations was approved by altered acetylation of histone H3. Our findings further support the validity of both the three hit concept and that of our animal model. Reversal of behavioral and functional-morphological anomalies by fluoxetine treatment supports the predictive validity of the model. This study highlights that early life stress does not only interact with the genetic and environmental factors, but has strong influence also on therapeutic efficacy.

Assessing the Impact of (Self)-Quarantine through a Basic Model of Infectious Disease Dynamics.

We introduce a system of differential equations to assess the impact of (self-)quarantine of symptomatic infectious individuals on disease dynamics. To this end we depart from using the classic bilinear infection process, but remain within the framework of the mass-action assumption. From the mathematical point of view, the model we propose is interesting due to the lack of continuous differentiability at disease-free steady states, which implies that the basic reproductive number cannot be computed following established mathematical approaches for certain parameter values. However, we parametrise our mathematical model using published values from the COVID-19 literature, and analyse the model simulations. We also contrast model simulations against publicly available COVID-19 test data, focusing on the first wave of the pandemic during March-July 2020 in the UK. Our simulations indicate that actual peak case numbers might have been as much as 200 times higher than the reported positive test cases during the first wave in the UK. We find that very strong adherence to self-quarantine rules yields (only) a reduction of 22% of peak numbers and delays the onset of the peak by approximately 30-35 days. However, during the early phase of the outbreak, the impact of (self)-quarantine is much more significant. We also take into account the effect of a national lockdown in a simplistic way by reducing the effective susceptible population size. We find that, in case of a 90% reduction of the effective susceptible population size, strong adherence to self-quarantine still only yields a 25% reduction of peak infectious numbers when compared to low adherence. This is due to the significant number of asymptomatic infectious individuals in the population.

Structured and unstructured continuous models for Wolbachia infections.

We introduce and investigate a series of models for an infection of a diplodiploid host species by the bacterial endosymbiont Wolbachia. The continuous models are characterized by partial vertical transmission, cytoplasmic incompatibility and fitness costs associated with the infection. A particular aspect of interest is competitions between mutually incompatible strains. We further introduce an age-structured model that takes into account different fertility and mortality rates at different stages of the life cycle of the individuals. With only a few parameters, the ordinary differential equation models exhibit already interesting dynamics and can be used to predict criteria under which a strain of bacteria is able to invade a population. Interestingly, but not surprisingly, the age-structured model shows significant differences concerning the existence and stability of equilibrium solutions compared to the unstructured model.

[CS circular staplers for rectal surgery--a multicenter prospective study]. / CS(R) körvarrógépek alkalmazása rectumanastomosisoknál--Multicentrikus prospektív klinikai vizsgálat.

While circular staplers are used worldwide - especially for rectal anastomoses - there are relatively few publications on the effectiveness of these instruments. Between May 2008 and March 2009 in a prospective multicenter surveillance study 136 patients were enrolled from nine surgical units in Hungary. Rectal anastomoses were performed mainly in the upper and middle third of the rectum. In 115 cases adenocarcinoma, in 16 patients other type of malignant tumors and in 5 cases with anastomosis in the distal third were estimated too. 20 laparoscopic and 116 "conventional" surgery was performed. 32 mm diameter type CS circular staplers were used in 50, 28 mm in 85, and 25 mm in one case. Intraoperative technical failure of the device occurred in four cases, immediate correction were performed successfully in all of these patients and they recovered without postoperative complications. Late anastomotic leaks were detected in five patients, of which three healed spontaneously and two required reoperation. In the whole series two patients died representing a 1.4 percent mortality rate. The CS circular staplers proved to be appropriate for infraperitoneal rectal anastomoses.

[Our experience with nephron-sparing surgery in the past nine years]. / A szervmegtartó vesemutétekkel szerzett tapasztalataink az elmúlt kilenc évben.

UNLABELLED: Surgical therapy is the only curative therapeutic approach for the treatment of renal cell carcinoma. Nephron-sparing surgery for renal cell carcinoma, when performed by proper indication, provides recurrence-free and long-term survival rates similar to those observed after a radical surgical procedure. AIM: In this retrospective study we present our experiences on open nephron-sparing surgery. We describe the rates of different indications of nephron-sparing surgery, the rates of different hystopathological findings, the complications and the long-term cancer specific survival rates. METHODS: We reviewed retrospectively the data of 33 patients who had nephron-sparing surgery with T1 tumors between 1999 and 2008 in our department. The last patients' status evaluation was carried out in March 2009. The mean follow up was 4.64 years. RESULTS: 82% of the patients had an elective indication, 3% had relative and 15% had absolute indication for nephron-sparing surgery procedure. The mean tumor greatest dimension was 2.86cm. The hystopathologic review revealed 94% clear cell, 6% papillary renal cell carcinomas in the class of malignant renal tumors. The 1- and 5-year cancer-specific survival chance were 93.8%. We had to do nephrectomy because of postoperative bleeding and urinoma in 3 cases. CONCLUSION: Nephron-sparing surgery is an acceptable and safe treatment that provides excellent long-term cancer specific survival rates for T1a renal cell carcinoma patients.

A dynamic model of CT scans for quantifying doubling time of ground glass opacities using histogram analysis.

We quantify a recent five-category CT histogram based classification of ground glass opacities using a dynamic mathematical model for the spatial-temporal evolution of malignant nodules. Our mathematical model takes the form of a spatially structured partial differential equation with a logistic crowding term. We present the results of extensive simulations and validate our model using patient data obtained from clinical CT images from patients with benign and malignant lesions.

Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.