Phosphorylation of Optineurin by protein kinase D regulates Parkin-dependent mitophagy.

Degradation of damaged mitochondria, a process called mitophagy, plays a role in mitochondrial quality control and its dysfunction has been linked to neurodegenerative pathologies. The PINK1 kinase and the ubiquitin ligase Parkin-mediated mitophagy represents the most common pathway in which specific receptors, including Optineurin (Optn), target ubiquitin-labeled mitochondria to autophagosomes. Here, we show that Protein Kinases D (PKD) are activated and recruited to damaged mitochondria.

Evaluation of the Performance and Tolerance of the Combination of an HA-based Filler with Tri-Hyal Technology and a Skin Biorevitalizer on Skin Aging Parameters.

Background: Biorevitalization solutions contain numerous nutritive compounds to improve skin quality. Dermal fillers like HA (hyaluronic acid), depending on rheological characteristics, are used to fill large static defaults with a sustained long-term efficacy. Treatments with either dermal filler or biorevitalization solutions alone are not enough to bring a global facial aging approach.

Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia.

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site.

Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia.

Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease.

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System.

Disturbed functional connectivity is assumed to cause neurocognitive deficits in patients suffering from schizophrenia. A Glutamate N-methyl-D-aspartate receptor (NMDAR) dysfunction has been suggested as a possible mechanism underlying altered connectivity in schizophrenia, especially in the gamma- and theta-frequency range. The present study aimed to investigate the effects of the NMDAR-antagonist ketamine on resting-state power, functional connectivity, and schizophrenia-like psychopathological changes in healthy volunteers.

Alterations of oscillatory neuronal activity during reward processing in schizophrenia.

Objectives: Reward system dysfunctions are considered to be a pathophysiological mechanism in schizophrenia. Electrophysiological studies of reward system functions have identified frequency-specific brain networks for the processing of positive (high-beta frequency) and negative (theta frequency) events. Remarkably, midbrain dopaminergic signalling also includes theta and high-beta frequency modes, which have been assumed to reflect tonic and phasic dopamine responses, respectively.

Mitochondrial Perturbations Couple mTORC2 to Autophagy in C. elegans.

Autophagy is stimulated by stress conditions and needs to be precisely tuned to ensure cellular homeostasis and organismal development and health. The kinase mechanistic target of rapamycin (mTOR) forms the enzymatic core of the highly conserved mTOR complexes mTORC1 and mTORC2. mTORC1 is a key inhibitor of autophagy, yet the function of mTORC2 in autophagy is controversial.

Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.

Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior.

Impact of physical or sexual childhood abuse on plasma DHEA, DHEA-S and cortisol in a low-dose dexamethasone suppression test and on cardiovascular risk parameters in adult patients with major depression or anxiety disorders.

While the impact of childhood trauma on basal and dynamic cortisol regulation has widely been studied, the most abundant steroid hormones dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S have received little attention in this context. One-hundred in-door patients suffering from major depression or an anxiety disorder filled in the Childhood Trauma Questionaire. A low dose dexamethasone suppression test (DST) measuring DHEA, DHEA-S and cortisol was performed.

Role of Optineurin in the Mitochondrial Dysfunction: Potential Implications in Neurodegenerative Diseases and Cancer.

Optineurin (Optn) is a 577 aa protein encoded by the gene. Mutations of are associated with normal tension glaucoma and amyotrophic lateral sclerosis, and its gene has also been linked to the development of Paget's disease of bone and Crohn's disease. Optn is involved in diverse cellular functions, including NF-κB regulation, membrane trafficking, exocytosis, vesicle transport, reorganization of actin and microtubules, cell cycle control, and autophagy.

Glutamatergic Deficits in Schizophrenia - Biomarkers and Pharmacological Interventions within the Ketamine Model.

Background: The observation that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists such as ketamine transiently induce schizophrenia-like positive, negative and cognitive symptoms has led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. NMDAR hypofunction can explain many schizophrenia symptoms directly due to excitatory-to-inhibitory (E/I) imbalance, but also dopaminergic dysfunction itself. However, so far no new drug targeting the NMDAR has been successfully approved.

Alterations in interhemispheric gamma-band connectivity are related to the emergence of auditory verbal hallucinations in healthy subjects during NMDA-receptor blockade.

Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers.

Tibial plateau fracture management: arthroscopically-assisted versus ORIF procedure - clinical and radiological comparison.

Introduction: Tibial plateau fractures are articular injuries that may influence final functional outcome of the knee. Although these fractures comprise only 1% of all fractures, the fracture pattern is usually complex and requires anatomical reduction and absolutely stable fixation to achieve satisfactory results. The development of knee osteoarthritis is a common late complication and it can be strongly influenced by additional, underestimated cartilage defects, and meniscal and ligament tears.

Surgical Treatment of Metastatic Disease of the Vertebral Column.

Spinal metastatic disease is a rather common occurrence and definitely warrants attention and treatment due to the high likelihood of leaving cancer patients severely disabled in their final months of life. Recent developments in the understanding of the behavior of different tumor types, as well as advances in surgical treatment, are allowing for the evolution of treatment algorithms, especially when surgical treatment is to be considered. This paper gives an overview of the decision-making process and the array of surgical options currently available.

Glutamatergic deficit and schizophrenia-like negative symptoms: new evidence from ketamine-induced mismatch negativity alterations in healthy male humans.

Background: Targeting the -methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine.

A laboratory exercise to illustrate protein-membrane interactions.

The laboratory protocol presented here takes about 3 hours to perform and investigates protein and lipid interactions. Students first purify His6 -tagged human apolipoprotein A-I (apoA-I) with Ni-NTA affinity resin in a simple batch protocol and prepare multilamellar vesicles (MLV) from pre-dried phospholipid films. When apoA-I is added to the MLV, much smaller protein/lipid nanodisc complexes are formed in some instances.

[Hip arthroscopy].

In the last ten years, hip arthroscopy has been developing intensively and it is rapidly gaining primacy in the treatment of various injuries and damages to the hip itself and its immediate vicinity. The basic advantage of hip arthroscopy surgery versus classic open surgery is avoiding an open dislocation of the hip and, thus, reducing patient's morbidity and accelerating his/her rehabilitation, which leads to a quicker return to everyday activities. The success of arthroscopic surgery depends on the correct indication for the surgery and on the experience and the skill of the operator.

Current practice variations in the management of anterior cruciate ligament injuries in Croatia.

Aim: To investigate current preferences and opinions on the diagnosis, treatment and rehabilitation of patients with anterior cruciate ligament (ACL) injury in Croatia.

Methods: The survey was conducted using a questionnaire which was sent by e-mail to all 189 members of the Croatian Orthopaedic and Traumatology Association. Only respondents who had performed at least one ACL reconstruction during 2011 were asked to fill out the questionnaire.

Curcumin acts anti-proliferative and pro-apoptotic in human meningiomas.

Meningiomas, the most frequent benign intracranial and intraspinal types of tumors are normally removed by surgery. Complications can occur when the tumor is critically localized and cannot be completely removed or when comorbidities of the mostly elder patients increase the general surgical risk. Thus, alternate medical treatment concepts for the therapy of meningiomas would be desirable.

Education in family medicine at the University of Mostar School of Medicine.

Department of Family medicine has been formed in academic year 2002/2003, few years later after the foundation of the School of Medicine University of Mostar. The formal members of department are professor and assistants who lecture and lead seminars. In addition, physicians in rural practices contribute to teaching of family medicine.

Treatment of lupus nephritis by mycophenolate mofetil.

Background/aims: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN.

Methods: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis.

Public health services in Herzegovina region during 1992-1995 war.

The aim of this study was to describe the situation and the development of Croatian Defense Council medical corps during the 1992-1995 war in Bosnia and Herzegovina. The paper provides an overview and describes the main events that lead to development of the medical care in the wartime conditions, with special emphasis on the public health system in Herzegovina region. This included the creation of three distinctive public health system settings: initial, integral and post-war period, all marked by certain specificities in organization and delivery of the public health and overall health care to both military and civilians.

Snakebites in Mostar region, Bosnia and Herzegovina.

The aim of this study was to provide an overview of the snakebites in patients hospitalized at the Mostar Clinical Hospital, admitted between 1983 and 2006. A total of 341 patients were recorded, with moderate men predominance (52.8%).

Prevalence of increased body weight and hypertension in the population of Croatian mainland and Adriatic Islands--are islanders really healthier?

The aim of this study was to compare the prevalence of the hypertension and the increased body weight (BMI) between Croatian mainland and Adriatic island population. The data from the Croatian Adult Health Survey (N = 9,070) served as an estimate for the mainland Croatian population, while the data from "1001 Dalmatian study" (N = 1,001) were collected from four Adriatic islands; Rab, Vis, Lastovo and Mljet. The prevalence of increased body weight and hypertension was calculated for the four age groups and analyzed using chi-square test.