Pre-Fracture Functional Status and Early Functional Recovery are Significant Predictors of Instrumental Activities of Daily Living After Hip Fracture: A Prospective Cohort Study.

Introduction: Although the overall quality of medicine has improved in recent decades, the functional capacity in many hip fracture patients remains insufficient. The goal of the present study was to identify significant predictors of Instrumental Activities of Daily Living (IADL) measured by the Lawton-Brody scale at 3- and 6-month follow-up in patients with hip fractures admitted to a hospital. Methods: This observational cohort study included 191 patients with acute hip fractures. IADL was measured at baseline and after 3 and 6 months using the Lawton-Brody scale. Multivariable logistic regression analysis was carried out using pre-fracture functional status, sociodemographic variables, hand grip strength (HGS), surgical procedure, complications, and length of hospital stay, Short Physical Performance Battery, and Barthel Index (BI) on the fifth postoperative day as potential predictors for IADL after a hip fracture surgery. Results: The mean age of the participants was 80.3 ± 6.8 years, and 77.0% of our cohort were women. Multivariate regression analysis revealed that pre-fracture functional status and early functional recovery were independent predictors of IADL after hip fracture surgery. Conclusions: Clinicians should take steps to improve functional outcomes by changing how patients are rehabilitated in the first days after hip fracture surgery, especially for the group of patients with a lower functional status before the fracture.

KCC2 rs2297201 Gene Polymorphism Might be a Predictive Genetic Marker of Febrile Seizures.

Introduction: Febrile seizures (FS) are the most common neurological disease in childhood. The etiology of FS is the subject of numerous studies including studies regarding genetic predisposition. Aim: The aim of the study was to analyze the association of TRPV1 rs222747 and KCC2 rs2297201 gene polymorphisms with the occurrence of FS. Materials and Methods: The study included 112 patients diagnosed with FS classified as simple febrile seizures (SFS) or complex febrile seizures (CFS). We analyzed selected polymorphisms of KCC2 and TRPV1 genes using the Real-time PCR method. Results: The CT and TT genotypes of the rs2297201 polymorphism of the KCC2 gene are significantly more common in the group of children with FS than the control group (p = .002) as well as the allele T of this polymorphism (p = .045). Additionally, genotypes CT and TT of the rs2297201 polymorphism of the KCC2 gene were more frequent in the group of children with CFS compared to the control group (p < .001). Different genotypes and alleles of the rs222747 TRPV1 gene polymorphism were not associated with the occurrence of febrile seizures or epilepsy, nor were associated with the occurrence of a particular type of febrile seizure (p = .252). Conclusion: These results indicate that the CT and TT genotypes, as well as the T allele of rs2297201 polymorphism of the KCC2 gene, could be a predisposing factor for the FS, as well as the occurrence of CFS.

A 12-week exercise program improves functional status in postmenopausal osteoporotic women: randomized controlled study.

BACKGROUND: Beside the importance of implementing physical activity in treatment of patients with osteoporosis, the multicomponent exercise program and assessment of its functional outcomes performed by five performance-based measures, have not been explored yet. AIM: The present study evaluated the effect of the 12 weeks exercise program on functional outcomes of postmenopausal patients with densitometric diagnosed osteoporosis. DESIGN: The study was designed as randomized control study. SETTING: Female outpatients with diagnosed postmenopausal osteoporosis were included in the study. POPULATION: The study included women from urban area. METHODS: Patients were randomized in two groups: exercise group (EG) and control group (CG). Patients in the exercise group (N.=47) participated in a 12 weeks exercise program, which consisted of resistance training, balance exercise and aerobic exercise, while patients from control group (N.=49) had not participated in any exercise program during the intervention period. Functional outcomes determined by Time Up and Go Test (TUG), Sit To Stand test (STS) and One Leg Stance Test (OLST) were evaluated at baseline and 4 and 12 weeks after treatment, while Fall Efficacy Scale (FES-I) and Knowledge About Osteoporosis Questionnaire (OKAT-S) were assessed at baseline and after 12 weeks, respectively. RESULTS: There were noticed statistically significant improvement in all observed measurements in EG after 4 and 12 weeks, respectively. Comparison between groups showed statistically significant difference in EG compared to CG in all functional outcomes in observed periods (P<0.001 for all). OLST significantly changed only in EG, not in CG, in both experimental periods. After 4 weeks, in CG there were no statistically significant changes in any of the monitored parameters, while after 12 weeks improvements were detected with TUG, STS, FES-I and OKAT-S. CONCLUSIONS: Twelve weeks exercise program, as an effective, inexpensive and easily performed method, improved functional status in postmenopausal osteoporotic women. CLINICAL REHABILITATION IMPACT: In the present study we found that supervised exercise program in postmenopausal osteoporotic female patients significantly improved their muscle strength and balance and decreased fear of falling. Thus, it is proposed to be a part of clinical protocol for osteoporosis treatment.

Effects of 12-Week Exercise Program on Enzyme Activity of Serum Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Female Patients with Postmenopausal Osteoporosis: A Randomized Control Study.

BACKGROUND: Osteoporosis is a disease characterized by decreased bone density and destruction of bone microarchitecture. Indicators for altered bone homeostasis are changes in the serum level of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The purpose of the current study was to evaluate the effect of a 12-week exercise program on enzyme activity of serum MMP-9 and TIMP-1 in postmenopausal osteoporotic patients. Materials and methods. Participants were randomized in two groups: exercise (EG) (N = 37) and control (CG) (N = 37) and control (CG) (. RESULTS: Significant differences between pretreatment and posttreatment enzyme activities of serum MMP-9 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (. CONCLUSION: Our results suggest that a 12-week exercise program has an influence on enzyme activity of serum MMP-9, revealing a possible role of MMPs in initiating training-specific adaptation. Although measurements of circulating MMP-9 and TIMP-1 allowed us to detect effects of exercise, as of today, they have no real role in the diagnosis of osteoporosis and/or follow-up of osteoporotic patient's response to treatment. MMP-9 might be used as an important prognostic marker for the evaluation of patient's response to exercise. Larger-randomized controlled studies need to be performed to expand this area of knowledge. This trial is registered with trial registration number: NCT03816449).

Autologous Fat Graft: Not Only an Aesthetic Solution.

Subcutaneous adipose tissue was defined as the "perfect filler" as is soft and malleable and is usually enough present in the body for correcting volume defects and small remodelling purposes. The first attempts to implant autologous adipose tissue dates back to the end of the twentieth century, and with the refinement of harvesting, processing and replanting techniques today a uniform and predictable amount of survival rate were achieved. Those improvements have led to wider use of autologous fat grafts in many medical specialities not only in aesthetic or reconstructive treatments.

Botulin Toxin Use in Scars/Keloids Treatment.

Botulinum toxin (BTX) is a neurotoxin protein derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions which include scar prevention and treatment with good results The complex mechanism underlying those results is not completely understood but several mechanisms were proposed release inhibition of different substances like (TGF)-ß, substance P, calcitonin gene-related peptide (CGRP) and glutamate thus modulating cutaneous inflammation and wound healing. We analysed the published data on BTX off label applications on scars and keloids retrieved from PubMed.

Botulin Toxin Use in Rosacea and Facial Flushing Treatment.

Botulinum toxin (BTX) is a neurotoxin derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions, which include Rosacea and facial flushing treatment with good results. The complex mechanism underlying those results is not completely understood but was proposed a release inhibition of acetylcholine from peripheral autonomic nerves of the cutaneous vasodilatory system combined with the blockade substance P and calcitonin gene-related peptide (CGRP) thus modulating blood vessel dilatation. We analysed the published data on BTX off label applications rosacea and flushing retrieved from PubMed.

Gut Microbiota and the Alteration of Immune Balance in Skin Diseases: From Nutraceuticals to Fecal Transplantation.

The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis.

The Impact of Immunological Factors on Depression Treatment - Relation Between Antidepressants and Immunomodulation Agents.

It is determined that 30% of patients with depression are resistant to antidepressant medication. The increased concentration of inflammation factors, such as C-reactive protein, and pro-inflammatory cytokines, have been detected in serum in these patients. It is necessary to establish new therapeutic possibilities and protocols that are created to overcome the difficulties caused by increased concentration of inflammatory biomarkers in depressive patients. The Selective Serotonin Reuptake Inhibitors (SSRIs) are considered to be the most powerful antidepressants, increasing the level of serotonin in endogenous depression, as well as in that caused by immunological mechanisms. It is believed that agents that influence cytokines, immunological signal pathways and cytokine syntheses, like the inhibitors of cyclooxygenase enzyme and other non-steroidal anti-inflammatory drugs (NSAIDs), are very important in the potential treatment of residual symptoms of depression. Treatment with cytokine antagonists is one of the potential adjuvant therapies, along with antidepressants. Signal pathways blockers, such as the inhibitors of cyclooxygenase and other NSAIDs, are in the phase of research, in terms of their antidepressant effects. Also, it has been shown that the inhibition of indolamin-2,3 deoxygenase (IDO) and kynurenine (KYN) signal pathways in the synthesis of neurotransmitters, by application of IDO antagonists, are leading to suppression of pro-inflammatory cytokine effects. Antidepressants may have anti-inflammatory effects, depending on dose and type, and they achieve this effect through the decrease of pro-inflammatory cytokine production and increase of anti-inflammatory cytokines. Also, antidepressants modulate the humoral and cellular immune system. This work aims to summarise certain neurobiological and neuroimmunological specificities that have been observed in patients with depression, antidepressants and immunomodulation agents. The understanding of complex and heterogenic pathophysiology of depression through the prism of the altered immune system, is of major importance, in terms of better optimisation of pharmacotherapy, and options for a personalised approach in depressive disorder treatment.

New Trends in Cutaneous Melanoma Surgery.

The main surgical treatment for melanoma consists in wide surgical excision of the primary lesion and the sentinel node but in recent times management of melanoma is rapidly evolving with the introduction of new systemic therapies, like BRAF inhibitors, MEK inhibitors and antibodies anti-PD-1 that show good results in controlling even advanced stages of the disease. This review aims to present data for the optimal surgical management of patients with malignant melanoma.

In Ovo Sexing of Chicken Eggs by Virus Spectroscopy.

Recently, some new methods for sexing of chicken eggs by fluorescence and Raman spectroscopy through the shell membrane have been proposed. On the other hand, in another investigation, a new virus medical imaging has been suggested. In this research, summing over these considerations, a new technique for sexing of chicken eggs by virus spectroscopy through the shell membrane is proposed. It is shown that viruses outside the shell of egg can communicate with materials inside it and determine the gender of chick embryo and it's evolutions.

DNA Waves and Their Applications in Biology.

AIM: In this research, we show that DNA waves have many applications in biology. DNA is formed by the joining of quantum particles like electrons and charged atoms. DNA has different motions during transcription, translation, and replication, in which the charged particles move, accelerate, and emit waves. Thus, DNA could emit quantum waves. METHODS: Two methods are proposed to observe the effect of DNA waves. The first proposed method measures DNA waves emitted by bacteria suspended in the milk. The vessel of milk is placed in the interior of an inductor. One side of the vessel is connected to a generator and another side to a scope. By sending a current to the inductor, an input electromagnetic field is produced. Bacteria interact with the input field, change it and produce new output signals. Using the scope, the output signals are observed and compared with the input signals. The number of DNA waves produced also depends on temperature. RESULTS: At lower temperatures, bacterial replication is less, and fewer DNA waves are produced. Conversely, more bacteria are generated at higher temperatures, and more DNA waves are produced. The second proposed method acquires and images of DNA signals of chick embryos. In this method, a circuit is constructed that consists of a graphene or metal tube, generator, inductor, scope, DNA in the interior of eggs and DNA exterior to the eggs. Magnetic waves pass the interior and exterior DNA as well as the graphene. The DNA is excited and the exciting interior/exterior DNA exchanges waves. Some of these waves interact with electrons in the graphene tube, and a current is generated. Properties of the chick embryo DNA can be explored by analysing changes in the waves that emerge from the eggs. CONCLUSION: It is concluded that DNA waves could be used extensively in imaging and provide for us the exact information about evolutions of DNAs interior of biological systems.

Beta Blockers and Melanoma.

Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by ß-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc. Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only ß3-but, not ß2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that ß-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma.

Psychotherapy Role in Treatment of Chronic Spontaneous Urticaria in a 32 Years Old Female Patient.

As indicated by the latest scientific evidence, the lines between different fields of medicine gradually blur and overlap more and more. Psychiatry and dermatology have seen this trend in the last decade as an ever-increasing number of studies suggest the strong connection of many dermatological syndromes and diseases with psychiatric conditions and vice versa. It seems that the relationship is more intertwined than previously believed and the effects of different multidisciplinary approaches to diagnostic and treatment are being considered. The aim of this case report is to highlight the effect of psychotherapy on chronic spontaneous urticaria which is tightly related to the maladaptive stress response.

A Mathematical Model for the Signal of Death and Emergence of Mind Out of Brain in Izhikevich Neuron Model.

AIM: In this paper, using a mathematical model, we will show that for special exchanged photons, the Hamiltonian of a collection of neurons tends to a constant number and all activities is stopped. These photons could be called as the dead photons. To this aim, we use concepts of Bio-BIon in Izhikevich Neuron model. METHODS: In a neuron, there is a page of Dendrite, a page of axon's terminals and a tube of Schwann cells, axon and Myelin Sheath that connects them. These two pages and tube form a Bio-Bion. In a Bio-Bion, exchanging photons and some charged particles between terminals of dendrite and terminals of axon leads to the oscillation of neurons and transferring information. This Bion produces the Hamiltonian, wave equation and action potential of Izhikevich Neuron model. Also, this Bion determines the type of dependency of parameters of Izhikevich model on temperature and frequency and obtains the exact shape of membrane capacitance, resting membrane potential and instantaneous threshold potential. RESULTS: Under some conditions, waves of neurons in this BIon join to each other and potential shrinks to a delta function. Consequently, total Hamiltonian of the system tends to a constant number and system of neuron act like a dead system. Finally, this model indicates that all neurons have the ability to produce similar waves and signals like waves of the mind. CONCLUSION: Generalizing this to biology, we can claim that neurons out of the brain can produce signals of minding and imaging and thus mind isn't confined to the brain.

Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study.

Febrile seizures (FS) are the most common neurological disorder in childhood and are a great stress for parents due to their dramatic clinical appearance. Using test for determination of homozygously recessive characteristics in humans (HRC test) we analyzed presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits among FS patients (N=121) and control (N=121) to determine a possible deviation in the homozygosity level and genetic loads in the group of affected children and whether there is a predisposition to the occurrence of FS. The results of our study show a statistically significant difference in the mean values of the HRC tested ( x¯HRC/20 CN = 3.2 ± 0.2; x¯HRC/20 FS = 4.6 ± 0.2, t= 5.74 , p< 0.0001), as well as in the distribution and variability of two studied samples (VC=55,3%, VFS= 39,6%), which indicates a complex polygenic difference among the tested groups of subjects. The differences in the degree of genetic homozygosity and variability are also present between the genders (t Cf/FSf = 4.12; t Cm/FSm = 3.98; p <0.0001) (VCf=56.9%, VFSf= 39.3%; VCm=54.1%, VFSm=40.1%). Obtained results indicate the enlargement of recessively homozygous genetic loads in the group of children with FS which may represent some kind of predisposition for expressivity of this type of seizures.

Nanoparticle-mediated p53 gene therapy for tumor inhibition.

The p53 tumor suppressor gene is mutated in 50% of human cancers, resulting in more aggressive disease with greater resistance to chemotherapy and radiation therapy. Advances in gene therapy technologies offer a promising approach to restoring p53 function. We have developed polymeric nanoparticles (NPs), based on poly (lactic-co-glycolic acid), that provide sustained intracellular delivery of plasmid DNA, resulting in sustained gene expression without vector-associated toxicity. Our previous studies with p53 gene-loaded NPs (p53NPs) demonstrated sustained antiproliferative effects in cancer cells in vitro. The objective of this study was to evaluate the efficacy of p53NPs in vivo. Tumor xenografts in mice were established with human p53-null prostate cancer cells. Animals were treated with p53NPs by either local (intratumoral injection) or systemic (intravenous) administration. Controls included saline, p53 DNA alone, and control NPs. Mice treated with local injections of p53NPs demonstrated significant tumor inhibition and improved animal survival compared with controls. Tumor inhibition corresponded to sustained and greater p53 gene and protein expression in tumors treated with p53NPs than with p53 DNA alone. A single intravenous dose of p53NPs was successful in reducing tumor growth and improving animal survival, although not to the same extent as with local injections. Imaging studies showed that NPs accumulate in tumor tissue after intravenous injection; however, further improvement in tumor targeting efficiency of p53NPs may be needed for better outcome. In conclusion, the NP-mediated p53 gene therapy is effective in tumor growth inhibition. NPs may be developed as nonviral vectors for cancer and other genetic diseases.

Optical imaging and magnetic field targeting of magnetic nanoparticles in tumors.

To address efficacy issues of cancer diagnosis and chemotherapy, we have developed a magnetic nanoparticle (MNP) formulation with combined drug delivery and imaging properties that can potentially be used in image-guided drug therapy. Our MNP consists of an iron-oxide magnetic core coated with oleic acid (OA) and stabilized with an amphiphilic block copolymer. Previously, we reported that our MNP formulation can provide prolonged contrast for tumor magnetic resonance imaging and can be loaded with hydrophobic anticancer agents for sustained drug delivery. In this study, we developed MNPs with optical imaging properties using new near-infrared dyes to quantitatively determine their long-term biodistribution and tumor localization with and without an external magnetic field in mice with xenograft breast tumors. MNPs localized slowly in the tumor, reaching a peak 48 h post-injection before slowly declining over the next 11 days. One hour exposure of the tumor to a magnetic field further enhanced MNP localization to tumors. Our MNPs can be developed with combined drug delivery and multimodal imaging properties to improve cancer diagnosis, provide sustained treatment, and monitor therapeutic effects in tumors over time.

Magnetic resonance imaging of multifunctional pluronic stabilized iron-oxide nanoparticles in tumor-bearing mice.

We are investigating the magnetic resonance imaging characteristics of magnetic nanoparticles (MNPs) that consist of an iron-oxide magnetic core coated with oleic acid (OA), then stabilized with a pluronic or tetronic block copolymer. Since pluronics and tetronics vary structurally, and also in the ratio of hydrophobic (poly[propylene oxide]) and hydrophilic (poly[ethylene oxide]) segments in the polymer chain and in molecular weight, it was hypothesized that their anchoring to the OA coating around the magnetic core could significantly influence the physical properties of MNPs, their interactions with biological environment following intravenous administration, and ability to localize to tumors. The amount of block copolymer associated with MNPs was seen to depend upon their molecular structures and influence the characteristics of MNPs. Pluronic F127-modified MNPs demonstrated sustained and enhanced contrast in the whole tumor, whereas that of Feridex IV was transient and confined to the tumor periphery. In conclusion, our pluronic F127-coated MNPs, which can also be loaded with anticancer agents for drug delivery, can be developed as an effective cancer theranostic agent, i.e. an agent with combined drug delivery and imaging properties.

3-D tumor model for in vitro evaluation of anticancer drugs.

The efficacy of potential anticancer drugs during preclinical development is generally tested in vitro using cancer cells grown in monolayer; however, a significant discrepancy in their efficacy is observed when these drugs are evaluated in vivo. This discrepancy, in part, could be due to the three-dimensional (3-D) nature of tumors as compared to the two-dimensional (2-D) nature of monolayer cultures. Therefore, there is a need for an in vitro model that would mimic the 3-D nature of tumors. With this objective, we have developed surface-engineered, large and porous biodegradable polymeric microparticles as a scaffold for 3-D growth of cancer cells. Using the MCF-7 cell line as model breast cancer cells, we evaluated the antiproliferative effect of three anticancer drugs: doxorubicin, paclitaxel and tamoxifen in 3-D model vs in 2-D monolayer. With optimized composition of microparticles and cell culture conditions, a density of 4.5 x 10 (6) MCF-7 cells/mg of microparticles, which is an 18-fold increase from the seeding density, was achieved in six days of culture. Cells were observed to have grown in clumps on the microparticle surface as well as in their interior matrix structure. The antiproliferative effect of the drugs in 3-D model was significantly lower than in 2-D monolayer, which was evident from the 12- to 23-fold differences in their IC 50 values. Using doxorubicin, the flow cytometry data demonstrated approximately 2.6-fold lower drug accumulation in the cells grown in 3-D model than in the cells grown as 2-D monolayer. Further, only 26% of the cells in 3-D model had the same concentration of drug as the cells in monolayer, thus explaining the reduced activity of the drugs in 3-D model. The collagen content of the cells grown in 3-D model was 2-fold greater than that of the cells grown in 2-D, suggesting greater synthesis of extracellular matrix in 3-D model, which acted as a barrier to drug diffusion. The microarray analysis showed changes in several genes in cells grown in 3-D, which could also influence the drug effect. In conclusion, the cells grown in 3-D are more resistant to chemotherapy than those grown in 2-D culture, suggesting the significant roles of cellular architecture, phenotypic variations, and extracellular matrix barrier to drug transport in drug efficacy. We propose that our model provides a better assessment of drug efficacy than the currently used 2-D monolayer as many of its characteristic features are similar to an actual tumor. A well-characterized 3-D model can particularly be useful for rapid screening of a large number of therapeutics for their efficacy during the drug discovery phase.