The Restoration of the Prearthritic Joint Line Does Not Guarantee the Natural Knee Kinematics: A Gait Analysis Evaluation Following Primary Total Knee Arthroplasty.

Background: Unrestricted kinematic alignment (uKA) in total knee arthroplasty (TKA) has the theoretical advantage of reproducing patients' constitutional alignment and restoring the pre-arthritic joint line position and obliquity. However, modifications of the original uKA technique have been proposed due to the potential risk of mechanical failure and instability. Given the significant variability in soft tissue behavior within the same bony morphology group, uKA pure knee resurfacing could be occasionally detrimental.

Chlorine isotopes constrain a major drawdown of the Mediterranean Sea during the Messinian Salinity Crisis.

Hydrological restriction from the Atlantic Ocean transformed the Mediterranean Sea into a giant saline basin during the Messinian Salinity Crisis (5.97-5.33 million years ago).

Boundaries in Kinematic Alignment: Why, When, and How.

The use of alternative alignments in total knee arthroplasty (TKA) has recently been increasing in popularity: many of these alignments have been included in the broad spectrum of "kinematic alignment." This alternative approach was recommended to increase patients' satisfaction since many studies based on patient-reported outcome measures (PROMs) showed that every fifth patient is not satisfied with the surgical outcome. In fact, the original kinematic alignment technique was designed as a "pure resurfacing" technique, maintaining the preoperative axes (flexion-extension and axial rotation) of the knee.

Multiplex PCR in septic arthritis and periprosthetic joint infections microorganism identification: Results from the application of a new molecular testing diagnostic algorithm.

Purpose: Pathogen identification is key in the treatment of septic arthritis (SA) and periprosthetic joint infections (PJI). This study evaluates the outcome of the application of a new, score-based SA and PJI diagnostic algorithm, which includes the execution of molecular testing on synovial fluid.

Methods: A score-based diagnostic algorithm, which includes serologic and synovial fluid markers determination using multiplex PCR (mPCR) and Next Generation Sequencing (NGS) molecular testing, has been applied to a consecutive series of patients with clinically suspected SA or PJI.

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation.

Asymmetric gap balancing improves knee kinematic following primary total knee arthroplasty.

Purpose: The purpose of this study was to demonstrate closer-to-normal knee kinematics following primary total knee arthroplasty (TKA) performed establishing asymmetric gap balancing intraoperatively.

Material And Method: Two age-, sex-, BMI-matched groups of patients underwent medially stabilized TKA because of isolated knee disease. Group A (12 patients) underwent "unrestricted" kinematic alignment (uKA) according to Howell while group B (15 patients) received robot-assisted "simplified" KA (sKA) with an alignment goal (Hip-Knee-Ankle axis-HKA) ± 5° respect to the mechanical axis.

Sex differences in neuromuscular and biological determinants of isometric maximal force.

Aim: Force expression is characterized by an interplay of biological and molecular determinants that are expected to differentiate males and females in terms of maximal performance. These include muscle characteristics (muscle size, fiber type, contractility), neuromuscular regulation (central and peripheral factors of force expression), and individual genetic factors (miRNAs and gene/protein expression). This research aims to comprehensively assess these physiological variables and their role as determinants of maximal force difference between sexes.

In-vitro Approaches to Investigate the Detrimental Effect of Light on Dopaminergic Neurons.

Our recent study revealed that fluorescent lamp light can penetrate deep into the brain of mice and rats leading to the development of typical histological characteristics associated with Parkinson's disease such as the loss of dopamine neurons in the substantia nigra. Monochromatic LED lights were thus used in this work to deepen our knowledge on the effects of the major wavelength peaks of fluorescent light on mouse and human dopaminergic cells. In particular, we exposed immortalized dopaminergic MN9D neuronal cells, primary cultures of mouse mesencephalic dopaminergic cells and human dopaminergic neurons differentiated from induced pluripotent stem cells (hiPSC) to different LED light wavelengths.

Histological and clinical analysis of knee cyclops lesions.

Background And Aim: Cyclops Syndrome, first described by Jackson and Schaefer in 1990, is known as a complication of anterior cruciate ligament reconstruction (ACLR). However further researches have demonstrated that cyclops can be present even without symptoms and/or in absence of ACLR, simply configuring itself as a lesion in patients with rupture of the native ligament.

Methods: This is a retrospective cohort study in which we report our experience of 13 cyclops lesions found between 126 patients during a primary arthroscopic ACLR.

GPCRs in Intracellular Compartments: New Targets for Drug Discovery.

The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional differences between cells. G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors, and their signal transduction is traditionally viewed as a chain of events initiated from the plasma membrane. Furthermore, their intracellular trafficking, internalization, and recycling were considered only to regulate receptor desensitization and cell surface expression.

Interaction of the preferential D agonist (+)PHNO with dopamine D-D receptor heterodimers and diverse classes of monoamine receptor: relevance for PET imaging.

(+)-4-Propyl-9-hydroxynaphthoxazine ((+)PHNO) is a high affinity, preferential dopamine D versus D agonist employed in view of its high specificity and excellent signal-to-noise ratio as a radiotracer for positron emission tomography (PET) imaging. Surprisingly, its profile at other classes of monoamine receptor remains undocumented. In addition to hD and hD receptors, (+)PHNO revealed high affinity at hD but not hD or hD receptors.

Ventilation of the abyss in the Atlantic sector of the Southern Ocean.

The Atlantic sector of the Southern Ocean is the world's main production site of Antarctic Bottom Water, a water-mass that is ventilated at the ocean surface before sinking and entraining older water-masses-ultimately replenishing the abyssal global ocean. In recent decades, numerous attempts at estimating the rates of ventilation and overturning of Antarctic Bottom Water in this region have led to a strikingly broad range of results, with water transport-based calculations (8.4-9.

Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics.

Schizophrenia was first described by Emil Krapelin in the 19th century as one of the major mental illnesses causing disability worldwide. Since the introduction of chlorpromazine in 1952, strategies aimed at modifying the activity of dopamine receptors have played a major role for the treatment of schizophrenia. The introduction of atypical antipsychotics with clozapine broadened the range of potential targets for the treatment of this psychiatric disease, as they also modify the activity of the serotoninergic receptors.

Heart failure, frailty, and pre-frailty: A systematic review and meta-analysis of observational studies.

Frailty is a syndrome characterized by reduced physiological reserves, increased vulnerability to stressors and adverse health outcomes. Frailty can change the prognosis and treatment approach of several chronic diseases, including heart failure (HF). The aim of this study was to conduct a systematic review and meta-analysis assessing the association of HF with frailty and pre-frailty.

Role of the time dependence of Boltzmann open probability in voltage-gated proton channels.

The modeling and simulation of experimental families of current-time (I-t) curves of dimeric voltage-gated proton channels and of proton-conducting voltage sensing domains (VSDs) with a minimum of free parameters requires the movement of protons to be controlled by the rate of increase of the Boltzmann open probability p over time in passing from the holding to the depolarizing potential. Families of I-t curves of protomers and proton-conducting VSDs can be satisfactorily fitted by the use of a single free parameter expressing the rate constant k for the increase of p over time. Families of I-t curves of dimeric H1 channels can be fitted by a model that assumes an initial proton current I flowing along the two monomeric units, while they are still operating separately; I is gradually replaced by a slower and more potential-dependent current I flowing when the two monomers start operating jointly under the control of the coiled-coil domain.

A New Threat to Dopamine Neurons: The Downside of Artificial Light.

Growing awareness of adverse impacts of artificial light on human health has led to recognize light pollution as a significant global environmental issue. Despite, a large number of studies in rodent and monkey models of Parkinson's disease have reported that near infrared light has neuroprotective effects on dopaminergic neurons, recent findings have shown that prolonged exposure of rodents and birds to fluorescent artificial light results in an increase of neuromelanin granules in substantia nigra and loss of dopaminergic neurons. The observed detrimental effect seems to be dependent on a direct effect of light on the substantia nigra rather than a secondary effect of the alterations of circadian rhythms.

Controls on the Isotopic Composition of Nitrite (δN and δO) during Denitrification in Freshwater Sediments.

The microbial reduction of nitrate, via nitrite into gaseous di-nitrogen (denitrification) plays a major role in nitrogen removal from aquatic ecosystems. Natural abundance stable isotope measurements can reveal insights into the dynamics of production and consumption of nitrite during denitrification. In this study, batch experiments with environmental bacterial communities were used to investigate variations of concentrations and isotope compositions of both nitrite and nitrate under anoxic conditions.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson's Disease.

Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson's disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology.

Depression and heart failure: an intricate relationship.

In patients with heart failure (HF), depression is common and associated with adverse outcomes such as reduced adherence to treatment, poor quality of life, increased hospitalizations and elevated mortality. Despite these adverse impacts, depression remain underdiagnosed in HF patients. We performed a target review of the literature to identify the association between HF and depression, to examine the mechanisms that link these two conditions and to identify instruments for an accurate diagnosis and treatment of depression in HF patients.

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016.

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis.

Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test.

On the interaction of the highly charged peptides casocidins with biomimetic membranes.

Casocidin I and II (CI and CII) are structurally related antimicrobial peptides made of 39 and 31 amino acids, respectively, which derive from natural proteolytic processing of α-casein and adopt an ordered α-helical structure in biomimetic membranes. Their putative membrane-permeabilizing activity was investigated at Hg-supported self-assembled monolayers (SAMs) and at tethered bilayer lipid membranes (tBLMs); the latter consisted of a monolayer of 2,3,di-O-phytanyl-sn-glycerol-1-tetraethylene-glycol-d,l-α lipoic acid ester thiolipid (DPTL), with a dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylserine (DOPS) monolayer on top of it. Interaction of CI and CII with these biomimetic membranes was studied by four electrochemical techniques at pH 3, 5.

Distinctive binding properties of the negative allosteric modulator, [H]SB269,652, at recombinant dopamine D receptors.

Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts in an atypical manner with dopamine D receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we characterized the binding of radiolabelled [H]SB269,652 to human dopamine D receptor stably expressed in Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD value of ≈ 1nM.

Fluorescent light induces neurodegeneration in the rodent nigrostriatal system but near infrared LED light does not.

We investigated the effects of continuous artificial light exposure on the mouse substantia nigra (SN). A three month exposure of C57Bl/6J mice to white fluorescent light induced a 30% reduction in dopamine (DA) neurons in SN compared to controls, accompanied by a decrease of DA and its metabolites in the striatum. After six months of exposure, neurodegeneration progressed slightly, but the level of DA returned to the basal level, while the metabolites increased with respect to the control.