Headless cannulated screw and external fixator in the treatment of type C distal femur fractures: Effect of early mobilization on clinical outcomes.

Distal femur fractures occur due to high-energy trauma in young patients and with low-energy traumas in osteoporotic elderly patients. Implants selected for use in the treatment of distal femur fracture should provide stable fixation and allow early mobilization especially at elder patients. We aimed to investigate the effects of the headless cannulated screw and external fixator combination on the early mobilization of the patients and postoperative complications. Twenty-one patients with Type C distal femur fracture were included in the study.The fracture lines were temporarily fixed with K wires. After the fracture reduction with headless cannulated screws a tubular external fixator with carbon fiber rods was applied to bridge the knee joint. The external fixators were removed at the 6th week follow-up, and the patients were forced to perform knee flexion as much as they could tolerate. The 6th month KSS scores of the patients were 44.3 (34-60) and the 18th month KSS scores were 77.5 (60-88).Preoperative VAS score was 8(7-10) and postoperative VAS score was 4(3-6).Knee flexion of the patients at 6th months was 95.9 (80-110 degrees) and at 6th months knee flexion was 114.5 (100-125 degrees). Superficial pin site infection was observed at 4 patients and regressed with antibiotic therapy. Combination of cannulated screws with an external fixator for joint restoration in type C distal femur fractures allows early mobilization and reduces postoperative morbidity.

Investigation of human ß-defensins 1, 2 and 3 in human saliva by molecular dynamics.

Human ß-defensins present in saliva have a broad spectrum of antimicrobial activities that work against infections in oral cavity. To provide a better understanding of these molecules' properties and functions at the molecular level, we have investigated and compared the important structural properties of human ß-defensin-1, -2 and -3 using molecular dynamics simulations. Our results have shown that human ß-defensin-3 has a more flexible structure in water than the other two because of its high hydrophilicity, low ß-sheet content and high repulsive forces between its charged residues. Moreover, we found that the location of the salt bridges is important in protein's stability in water. Molecular dynamics simulations of human ß-defensins 1, 2 and 3 revealed that the hbd-3 is more flexible in water than hbd-1 and hbd-2.

Array-Based Comparative Genomic Hybridization Analysis in Children with Developmental Delay/Intellectual Disability.

Developmental delay (DD) is a condition wherein developmental milestones and learning skills do not occur at the expected age range for patients under 5 years of age. Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and cause-effect relationships. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Array-based comparative genomic hybridization aCGH) can detect copy number variations (CNVs) on the whole genome at higher resolution than conventional cytogenetic methods. The diagnostic yield of aCGH was 15.0-20.0% in DD/ID cases. The aim of this study was to discuss the clinical findings and aCGH analysis results of isolated and syndromic DD/ID cases in the context of genotype-phenotype correlation. The study included 139 cases (77 females, 62 males). Data analysis revealed 38 different CNVs in 35 cases. In this study, 19 cases with pathogenic CNVs (13.6%) and five cases with likely pathogenic CNVs (3.5%) were found in a total of 139 cases diagnosed with DD/ID. When all pathogenic and likely pathogenic cases were evaluated, the diagnosis rate was 17.1%. The use of aCGH analysis as a first-tier test in DD/ID cases contributes significantly to the diagnosis rates and enables the detection of rare microdeletion/microduplication syndromes. The clear determination of genetic etiology contributes to the literature in terms of genotype-phenotype correlation.

A comparison of peptide amphiphile nanofiber macromolecular assembly strategies.

Supramolecular peptide nanofibers that are composed of peptide amphiphile molecules have been widely used for many purposes from biomedical applications to energy conversion. The self-assembly mechanisms of these peptide nanofibers also provide convenient models for understanding the self-assembly mechanisms of various biological supramolecular systems; however, the current theoretical models that explain these mechanisms do not sufficiently explain the experimental results. In this study, we present a new way of modeling these nanofibers that better fits with the experimental data. Molecular dynamics simulations were applied to create model fibers using two different layer models and two different tilt angles. Strikingly, the fibers which were modeled to be tilting the peptide amphiphile molecules and/or tilting the plane were found to be more stable and consistent with the experiments.

Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers.

Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.

Alkaline Phosphatase-Mimicking Peptide Nanofibers for Osteogenic Differentiation.

Recognition of molecules and regulation of extracellular matrix synthesis are some of the functions of enzymes in addition to their catalytic activity. While a diverse array of enzyme-like materials have been developed, these efforts have largely been confined to the imitation of the chemical structure and catalytic activity of the enzymes, and it is unclear whether enzyme-mimetic molecules can also be used to replicate the matrix-regulatory roles ordinarily performed by natural enzymes. Self-assembled peptide nanofibers can provide multifunctional enzyme-mimetic properties, as the active sequences of the target enzymes can be directly incorporated into the peptides. Here, we report enhanced bone regeneration efficiency through peptide nanofibers carrying both catalytic and matrix-regulatory functions of alkaline phosphatase, a versatile enzyme that plays a critical role in bone formation by regulating phosphate homeostasis and calcifiable bone matrix formation. Histidine presenting peptide nanostructures were developed to function as phosphatases. These molecules are able to catalyze phosphate hydrolysis and serve as bone-like nodule inducing scaffolds. Alkaline phosphatase-like peptide nanofibers enabled osteogenesis for both osteoblast-like and mesenchymal cell lines.

Candesartan mediates microcirculation in acute necrotizing pancreatitis.

AIM: In the present study we aimed to determine the effect of an AT-II antagonist candesartan on pancreatic microcirculation in an experimental model of acute necrotizing pancreatitis. MATERIALS AND METHODS: There were five study groups with 10 animals in each. Pancreatitis was induced by intravenous infusion of cerulein and coadministration of glycodeoxycholate into biliopancreatic canal. Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups, respectively. At 24th and 48th hours; following anaesthesia laparotomy was performed and laser Doppler flowmetry was performed in the pancreatic tissue of the animals. Following scarification blood samples were obtained for amylase, myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the pancreas were obtained for histopathological analysis, endothelial cell apoptosis (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry. RESULTS: Pancreatic microcirculation was higher in the candesartan treated groups (p < 0.05). Myeloperoxidase, IL-6 and tumour necrosis factor alpha was found to be lower in the candesartan treated groups (p < 0.05). The pancreatic edema and inflammation were found to be reduced in the candesartan treated groups (p < 0.05). Endothelial apoptosis was found to be reduced by cadesartan treatment but it did not reach statistical significance (p > 0.05). Tissue matrix metalloproteinase -9 levels were found to be reduced with candesartan treatment (p < 0.05). CONCLUSION: Treatment with candesartan in the early phases of acute necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab. 3, Fig. 6, Ref. 28).

Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations.

A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. We also found that the S1 domain is more flexible than the S2 domain. We propose which of the experimentally observed glycans found on the spike may be more functional than the others. Detailed understanding of glycans is key for the development of new therapeutic strategies.

Emergency coronary artery bypass surgery in octogenarians with acute coronary syndrome: off and on pump.

OBJECTIVE: The risk of operation in cardiac surgery increases logarithmically with advanced age. In older individuals, additional comorbidities compel the clinician to deal with postoperative complications. The mortality and morbidity rates of emergency coronary artery bypass surgery (CABG) in the presence of acute coronary syndrome (ACS), or just after it, are higher than those of elective surgeries. In our study, we compared the outcomes of off-pump coronary bypass (OPCAB) and on-pump coronary bypass surgery (ONCAB) in this high-risk subgroup. PATIENTS AND METHODS: 383 octogenarians who underwent isolated emergency CABG due to ACS were divided into two groups according to the coronary bypass technique. Group 1 (off-pump) median age (IQR) 84 years (min: 80-max: 99, n = 130); Group 2, (on-pump) median age 85 years (min: 80-max: 89, n=253). Preoperative, intraoperative, and postoperative data were collected retrospectively on standard variables. OPCAB and ONCAB outcomes were compared. RESULTS: ONCAB patients had a significantly longer intensive care unit stay, longer hospital stay, more transfused erythrocyte suspension, more low cardiac output syndrome and acidosis, a higher rate of acute renal failure and a higher rate of stroke than OPCAB patients (respectively; p=0.003; p=0.008; p=0.002; p=0.031; p=0.038, p=0.022, respectively). CONCLUSIONS: We showed that emergency OPCAB as a revascularization option in elderly patients with acute coronary syndrome is more advantageous in terms of preventing major postoperative complications.

Amyloid inspired self-assembled peptide nanofibers.

Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force-distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies.

Bone deformities in patients with neurofibromatosis type 1: Single-center experience.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is the most common neurocutaneous syndrome with an autosomal dominant inheritance. However, half of the cases are de novo mutations. Involvement of bone, skin (cafe au lait macules), as well as ocular and tumoral formations is also associated with NF-1. Here, we present our case series of patients with bone deformities. METHODS: The medical files of patients with NF-1 who were followed up by the same doctor in the pediatric neurology outpatient clinic over 2 years were retrospectively analyzed. RESULTS: Overall, 19 girls and 13 boys were diagnosed with NF-1. Of these 32 patients, 12 (nine girls, three boys) were found to have bone pathologies. The average age was of these patients with bone pathology was 7.5 and 9.5 years. Scoliosis, bowing, short stature, and long bone cysts were found in descending order of frequency. Severe adhesions in the hands and feet as well as phalangeal hypoplasia were noted in one patient. CONCLUSION: NF-1 requires a multidisciplinary approach. Routine follow-up is very important as it is known that deformities that affect different systems may appear or increase with age. Severe hand and foot anomalies seen in one of our patients did not seem to be associated with NF-1.

Prognostic significance of Tp-e interval and Tp-e/QTc ratio in patients with COVID-19.

OBJECTIVE: Ventricular arrhythmias were the most frequent manifestations in patients with COVID-19. Both the natural course of the disease and the treatment drugs used have effects on ventricular repolarization. The objective of this study was to evaluate the effects of repolarization parameters obtained from surface electrocardiography (ECG) on prognosis. PATIENTS AND METHODS: Participants were 205 consecutive patients hospitalized with COVID-19 diagnosis. The 12-lead surface ECG was obtained from each patient on admission. The ECG results were evaluated against the patients' clinical characteristics and outcomes by experienced cardiology specialists. RESULTS: The mean age was higher in the non-survivor group compared to the survivor group (57.4 ± 15.7 vs. 65.6 ± 16.6; p = 0.001). The demographical characteristics were similar between the survivor and non-survivor groups. Multivariate analyses demonstrated that age (OR: 1.041; p = 0.009), D-dimer (OR: 1.002; p = 0.031), high-sensitivity troponin I (hs-TnI) (OR: 1.010; p = 0.041), pneumonia on computed tomography (CT) (OR: 4.985; p < 0.001), the peak-to-end interval of the T wave (Tp-e) (OR: 3.421; p < 0.001), and Tp-e/QTc ratio (OR: 1.978; p = 0.013) were statistically significant independent predictors in terms of determining mortality. CONCLUSIONS: Prolonged Tp-e interval and increased Tp-e/QTc ratio on admission are decent predictors and linked with mortality. ECG is a practical study to evaluate prognosis and potential arrhythmias, as well as initiating suitable treatment.

Efficacy and toxicity of preoperative chemotherapy with docetaxel and epirubicin in locally advanced invasive breast cancer.

PURPOSE: To investigate the efficacy and safety of neoadjuvant chemotherapy with docetaxel plus epirubicin with granulocyte colony-stimulating factor (G-CSF) support in locally advanced breast cancer patients. METHODS: We retrospectively evaluated the records of 39 patients with locally advanced breast cancer. All of them received neoadjuvant epirubicin 75 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks with G-CSF support. Responding patients were subjected to breast-conserving or modified radical mastectomy. RESULTS: Four (10.3%) patients achieved clinical complete response (cCR) and 25 (64.1%) clinical partial response (cPR). Pathologic complete response (pCR) was observed in 4 patients with cCR. Ten (25.6%) patients achieved stable disease (SD), while no patient had progressive disease (PD). Grade 3 and 4 neutropenia was observed in 6 (15.3%) and 4 cases (10.3%), respectively. Febrile neutropenia was observed in 2 (5.1%) cases and anemia in 7 (17.9%) cases. Grade 1/2 mucositis was observed in 12 (30.7%) patients and grade 1/2 peripheral neuropathy in 7 (17.9%) patients. Dose reduction was necessary in 4 patients with grade 4 neutropenia. The median disease-free survival was 60 months (95% CI: 41-79 months). Median overall survival was not reached. Five-year overall survival was 64.2%. CONCLUSION: The combination of docetaxel plus epirubicin was active and tolerable in neoadjuvant treatment of locally advanced breast cancer.

Carbon monoxide intoxication in geriatric patients: How important are lactate values at admission?

PURPOSE: The aim of this study was to investigate the demographic and clinical characteristics and treatment modalities of elderly patients with carbon monoxide (CO) intoxication. The secondary aim was to evaluate the importance of plasma lactate values in the diagnosis of acute CO intoxication in geriatric patients. METHODS: Data on geriatric patients who were admitted to the emergency department of Atatürk University Medical Faculty between January 2013 and April 2016 were analyzed retrospectively. RESULTS: Of the 197 cases included in the study, 97 were in the intoxication group and 100 were in the control group; 82.5% of the intoxication cases had mild neurological symptoms and 17.5% had severe neurological symptoms. Carboxyhemoglobin levels were significantly higher in patients with severe neurological symptoms (p = 0.031). All patients with severe neurological symptoms received hyperbaric-oxygen therapy (p < 0.001). In the intoxication group, lactate levels were significantly higher than in the control group (p = 0.001). The specificity for lactate 4 mmol/L and above was found as 98.0% with a positive predictive value and negative predictive value of 84.5% and 53.3%, respectively. CONCLUSION: High initial lactate levels may be a guide for cases with nonspecific symptoms in geriatric patients with suspected CO intoxication.

A patient with occult breast cancer presenting with an axillary lymph node metastasis and a synchronous contralateral breast cancer.

Detection of a breast mass accompanied by a contralateral axillary lymphadenopathy presents a dilemma because of the possible presence of an occult breast cancer on the same side as the axillary lymphadenopathy. A patient presented with an axillary lymphadenopathy from an occult breast cancer and a synchronous contralateral breast cancer, for which the differential diagnosis was established through a significant difference in estrogen and progesterone receptor levels. The patient was treated with neoadjuvant chemotherapy followed by bilateral modified radical mastectomy, adjuvant chemotherapy, and adjuvant radiation therapy. She is alive and free of disease 1.5 years after the diagnosis.

Selective adrenergic agonists and colon motility in monkeys.

Sympathetic stimulation during and after laparotomy and other surgical procedures may be a factor inducing postoperative ileus. In experiments conducted in fasting monkeys, the effects of the selective sympathetic agonists alpha 1 (phenylephrine), alpha 2 (ST-91), beta 1 (dobutamine), and beta 2 (terbutaline) on colon contractile activity were measured. Strain gauges were implanted on the colon. Recordings were made for 1 hour (control) and then for an additional hour during continuous infusion by one of a range of doses of each drug (experimental). The drug doses were chosen to cover both physiologic and pharmacologic concentrations. All of the sympathetic agonists caused a dose-dependent decrease in the frequency of colon contractions. The beta-agonists did so at a concentration that is sufficiently low to support a hypothesis that beta-stimulation leading to inhibition of smooth-muscle contraction may play an important role in the genesis of postoperative ileus.

Morphine effects on human colonic myoelectric activity in the postoperative period.

Colonic myoelectrical activity was studied in 25 patients, 18 of whom received morphine sulfate, using bipolar electrodes placed in the ascending and descending colon during laparotomy. Baseline myoelectrical activity was recorded daily, then morphine (3 to 15 mg) was administered intravenously, intramuscularly, or epidurally, and recordings continued. Seven activity patterns were observed during recovery from postoperative ileus. During the first 2 postoperative days, morphine at any dose did not affect colon myoelectrical activity. From the third postoperative day on, morphine given intravenously or intramuscularly initiated clusters of short, nonmigrating, phasic spike bursts occurring on each successive slow wave in 14 of 18 patients, which lasted for 30 to 45 minutes. When morphine was administered epidurally, there was no colonic response in any patient. These findings suggest that: (1) morphine intravenously or intramuscularly induces predominantly nonmigrating colonic spike bursts; (2) morphine-induced activity alters the normal pattern of colonic motility during recovery from postoperative ileus; and (3) these phenomena are not due to direct action of morphine on the spinal cord since epidural morphine had no effect.

Cisplatin plus vinorelbine as a salvage regimen in refractory breast cancer.

AIMS AND BACKGROUND: Breast cancer refractory to known effective agents is one of the major clinical problems frequently encountered in practice. Cisplatin and vinorelbine are known to be active drugs in anthracycline-refractory cases. In this phase II study, the effectiveness and tolerability of cisplatin and vinorelbine was investigated when used in combination as a salvage regimen in the treatment of metastatic refractory breast cancer. STUDY DESIGN: Twenty-four patients with advanced refractory breast cancer who had been previously treated with a regimen containing doxorubicin were included in the study. Six of the 24 patients also received taxanes after failure of doxorubicin. Cisplatin at 80 mg/m2 on day 1 and vinorelbine at 25 mg/m2 on days 1 and 8 were given every 3 weeks. RESULTS: A total of 98 cycles of chemotherapy was given, with a median of 4/patient. The response rate was 25% (2 [8.3%] complete and 4 [16.7%] partial responses). The median survival rates were 14 months in responders and 5.5 months in nonresponders (P = 0.0282). One complete and one partial response were observed in patients previously treated with paclitaxel (overall response rate, 33%). The median response duration was 12.5 mo (range, 4-21) in complete and 4.5 mo (range, 1.5-13) in the partial response group. Grade 3 and 4 neutropenia occurred in 9 patients, with no toxic deaths. Grade 2-3 nausea and vomiting in 6 patients and grade 1 neuropathy in 1 patient were noted. CONCLUSIONS: Although the number of cases is insufficient to indicate that the combination will be effective, it is noteworthy in consideration of anthracycline and taxane refractory cases. A combination of cisplatin and vinorelbine seems to be a reasonable and acceptable choice as an alternative salvage regimen in such cases.

Protective effect of a lipoxygenase inhibitor, nordihydroguaretic acid, on the ileal motor disturbances induced by Serratia marcescens endotoxin in rats.

This study was conducted to examine the effects of peptidoleukotrienes on the ileal contractility disturbances induced by Serratia marcescens endotoxin in rats. Thirty-two male Wistar rats were divided into four groups (n = 8 each). The first group was given only an anesthetic agent (control group); the second group was given the endotoxin (endotoxin group); the third group was given a lipoxygenase inhibitor, nordihydroguaretic acid (NDGA); and the fourth group was given NDGA 10 min before administration of the endotoxin (NDGA+endotoxin group). The isolated ileum response was recorded in each group. Normal contractile activity was seen in the control group. After the endotoxin was given. the isolated ileum did not respond to 497acetylcholine (ACh) in the endotoxin group, but the contractile results of isolated ileum to ACh were similar to the control group results in both the NDGA and endotoxin+NDGA groups. The results of this study demostrate that leukotrienes may play a role in endotoxin-induced ileal contractility disturbances, and that the lipoxygenase inhibitor, NDGA, could be useful for the treatment of ileal motility disturbances induced by endotoxin.