Total femoral spanning for distal femur "fragility" fractures utilising nail-plate fixation "short-term experience of a district general hospital".

PURPOSE: Our primary objective was to investigate the time to radiological union following linked nail-plate fixation of distal femur "fragility" fractures. Secondary objectives were to evaluate all-cause reoperations, 90-day mortality, rate of blood transfusion and the impact on quality of life. METHODS: In this retrospective study of all adults (≥ 65 years) with native or periprosthetic distal femur fragility fractures, underwent a linked nail-plate fixation, data were retrieved on fracture classifications, clinical frailty score, blood transfusion, length of hospital stay, 90-day mortality, time to radiological union, overall complication rates and EuroQoL-5D. RESULTS: In total, 18 out of 23 patients completed sequential follow-up. Radiological union was observed in 14 patients (median 143 days; range 42-414). Three patients underwent reoperations. There were no implant failures or a subsequent periprosthetic fractures. Ninety-day mortality was 17.4%. Eighteen patients required blood transfusion. The QoL was significantly lower after index surgery (0.875 vs. 0.684; p < 0.01). CONCLUSION: Based on our observation, with short-term follow-up, the linked nail-plate yields optimal stability to allow immediate weight bearing, in a cohort with moderate frailty. It is reproducible, with variable radiological union rates. The concept of "total femoral spanning" reduces the risk of subsequent periprosthetic fractures. The additional intervention has increased the rates of allogenic blood transfusion. There is significant impact on overall QoL, with almost 50% being more dependent in self-care.

Efficacy of biocompatible trilayers nanofibrous scaffold with/without allogeneic adipose-derived stem cells on class II furcation defects of dogs' model.

OBJECTIVE: This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. MATERIALS AND METHODS: After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. RESULTS: In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. CONCLUSIONS: The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. CLINICAL RELEVANCE: The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation.

Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2.

Impact of the COVID-19 pandemic on endoscopic retrograde cholangiopancreatography: a single center experience.

BACKGROUND: the COVID-19 pandemic has impacted on several aspects of health care services worldwide. The aim of the study was to determine its influence on the case volume, success rate and complication rate of endoscopic retrograde cholangiopancreatography (ERCP). METHOD: all patients who underwent ERCP one-year before and after applying COVID-19 safety measures at the Qena University Hospital were included. Data were collected from the patients' records, analyzed and compared. RESULTS: a total of 250 patients underwent ERCP between April 1st, 2019 and March 31st, 2021, and the mean age of participants was 52 ± 18 years. There was a 5 % increase in case volume after applying COVID-19 safety measures (128 vs 122) and the total procedure time was significantly shorter (42 vs 46 minutes, p = 0.04). There was no significant difference in the overall success rate and complication rate. Procedure success significantly correlated with cannulation attempts and total procedure time in both groups, and serum bilirubin and cannulation time in the pre-COVID-19 patients and alkaline phosphatase (ALP) in post-COVID patients. ERCP-related complications significantly correlated with cannulation attempts in both groups, and ALP, international normalized ratio (INR), cannulation time and total procedure time in pre-COVID-19 patients, and platelet count and amylase in post-COVID patients. Two patients were confirmed COVID-19 cases at the time of ERCP; therapeutic targets were achieved in both with a smooth post-ERCP recovery. Three out of nine ERCP team members caught a mild to moderate COVID-19 infection and recovered after receiving proper management. CONCLUSION: our result show that there was no negative impact of using COVID-19 safety measures and precautions on the case-volume, indications, overall outcome or complication rate of ERCP.

Intrastructural Help: Harnessing T Helper Cells Induced by Licensed Vaccines for Improvement of HIV Env Antibody Responses to Virus-Like Particle Vaccines.

Induction of persistent antibody responses by vaccination is generally thought to depend on efficient help by T follicular helper cells. Since the T helper cell response to HIV Env may not be optimal, we explored the possibility of improving the HIV Env antibody response to virus-like particle (VLP) vaccines by recruiting T helper cells induced by commonly used licensed vaccines to provide help for Env-specific B cells. B cells specific for the surface protein of a VLP can internalize the entire VLP and thus present peptides derived from the surface and core proteins on their major histocompatibility complex class II (MHC-II) molecules. This allows T helper cells specific for the core protein to provide intrastructural help for B cells recognizing the surface protein. Consistently, priming mice with an adjuvanted Gag protein vaccine enhanced the HIV Env antibody response to subsequent booster immunizations with HIV VLPs. To harness T helper cells induced by the licensed Tetanolpur vaccines, HIV VLPs that contained T helper cell epitopes of tetanus toxoid were generated. Tetanol-immunized mice raised stronger antibody responses to immunizations with VLPs containing tetanus toxoid T helper cell epitopes but not to VLPs lacking these epitopes. Depending on the priming immunization, the IgG subtype response to HIV Env after the VLP immunization could also be modified. Thus, harnessing T helper cells induced by other vaccines appears to be a promising approach to improve the HIV Env antibody response to VLP vaccines.IMPORTANCE Induction of HIV Env antibodies at sufficient levels with optimal Fc effector functions for durable protection remains a challenge. Efficient T cell help may be essential to induce such a desirable antibody response. Here, we provide proof of concept that T helper cells induced by a licensed vaccine can be harnessed to provide help for HIV Env-specific B cells and to modulate the Env-specific IgG subtype response.

Is the hepatocyte ultrastructural zonal heterogeneity changed by overnight (16 h) fasting? Morphometric study.

Background and objectives: Hepatocyte ultra-structure is influenced by feeding status, circadian rhythm, and zone location. The goal of the present study was to study the effect of overnight fasting on the hepatocyte ultrastructure and the zonal heterogeneity and to discuss the functional correlation.Methods: A total of 14 male albino rats were divided into two groups: negative control group fed ad libitum and overnight fasting rats for 16 hours. The different subcellular structures of both centrilobular and periportal hepatocytes in both control and fasted groups were compared by transmission electron microscopy. Morphometric analysis of the electron micrographs was also done using imageJ software.Results: The lysosomes surface density, mitochondrial volume and surface densities were significantly higher in periportal hepatocytes however surface density of smooth endoplasmic reticulum (SER) and peroxisomes were significantly higher in centrilobular hepatocytes of the control group. Fasting caused a significant decrease in the surface density of rough endoplasmic reticulum and glycogen volume density but with significant increase in SER surface density with more mitochondrial fusion and stronger mitochondrial ER contacts, isolation membranes, and autophagosomes. The zonal differences were maintained after fasting. The organelles appeared normal with no signs of degeneration.Conclusion: The organelles appeared normal with no signs of degeneration and the zonal differences were maintained after fasting. The change in hepatocyte ultrastructure after fasting may be related to autophagy.

Assessment of wound healing activity in diabetic mice treated with a novel therapeutic combination of selenium nanoparticles and platelets rich plasma.

Diabetic wound healing is sluggish, often ending in amputations. This study tested a novel, two-punch therapy in mice-Selenium nanoparticles (Se NPs) and platelet-rich plasma (PRP)-to boost healing. First, a mouse model of diabetes was created. Then, Se NPs were crafted for their impressive antioxidant and antimicrobial powers. PRP, packed with growth factors, was extracted from the mice's blood. Wound healing was tracked for 28 days through photos, scoring tools, and tissue analysis. Se NPs alone spurred healing, and PRP added extra fuel. Furthermore, when used in combination with PRP, the healing process was accelerated due to the higher concentration of growth factors in PRP. Notably, the combination of Se NPs and PRP exhibited a synergistic effect, significantly enhancing wound healing in diabetic mice. These findings hold promise for the treatment of diabetic wounds and have the potential to reduce the need for lower limb amputations associated with diabetic foot ulcers. The innovative combination therapy using Se NPs and PRP shows great potential in expediting the healing process and addressing the challenges of impaired wound healing in individuals with diabetes. This exciting finding suggests this therapy could change diabetic wound management, potentially saving limbs and improving lives.

A unilateral partial duplication of a fetal variant posterior cerebral artery associated with anomalous origin of duplicated superior cerebellar artery: a case report.

Variations at the junction of embryonic internal carotid and vertebrobasilar systems are rare and associated with a high incidence of stroke. During cadaver dissection, we demonstrated for the first time a case of hypoplastic right vertebral artery associated with partial duplication of the distal part of the right P1 segment of a partial fetal posterior cerebral artery (FPCA) and bilateral duplication of superior cerebellar arteries (SCAs), of which, the upper right SCA originated from PCA. We hypothesize that the poor development of the right half of the vertebrobasilar system caused the persistence of FPCA with anomalous origin of the right upper SCA as well as partial duplication of P1 segment of PCA as a remnant of the weak anastomosis between the embryonic right PCA and the basilar system. Such complex variations provide a huge challenge in their diagnosis and in choosing the suitable treatment modality for the stroke.

The role of stinging nettle (Urtica dioica L.) in the management of rotenone-induced Parkinson's disease in rats.

Parkinson's disease (PD) is one of the most common neurodegenerative conditions. Alpha-synuclein deposition, Lewy bodies (LBs) formation, disruption of the autophagic machinery, apoptosis of substantia nigra dopaminergic neurons, oxidative stress, and neuroinflammation are all pathologic hallmarks of PD. The leaves of the stinging Nettle (Urtica dioica L.) have a long history as an herbal cure with antioxidant, anti-inflammatory, anti-cancer, immunomodulatory, and neuroprotective properties. The current study aims for the first time to investigate the role of Nettle supplementation on Rotenone-induced PD. Rats were divided into five groups; a Saline control, Nettle control (100 mg/kg/day), Rotenone control (2 mg/kg/day), Rotenone + Nettle (50 mg /kg/day), and Rotenone + Nettle (100 mg/kg). After four weeks, the rats were examined for behavioral tests. The midbrains were investigated for histopathological alteration and immunohistochemical reaction for Tyrosine hydroxylase in the dopaminergic neurons, α-synuclein for Lewy bodies, caspase 3 for apoptotic neurons, LC3 and P62 for autophagic activity. Midbrain homogenates were examined for oxidative stress markers. mRNA expression of TNFα and Il6; inflammatory markers, Bcl-2, BAX and Caspase 3; apoptosis markers, were detected in midbrains. The results showed that Nettle caused recovery of midbrain dopaminergic neurons, by inhibiting apoptosis, inflammation, and oxidative stress and by restoring the autophagic machinery with clearance of α-synuclein deposits. We can conclude that Nettle is a potentially effective adjuvant in the treatment of Parkinson's disease.

Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system.

Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.

Harnessing immunoinformatics for developing a multiple-epitope peptide-based vaccination approach against SARS-CoV-2 spike protein.

COVID-19 has spread to over 200 countries with variable severity and mortality rates. Computational analysis is a valuable tool for developing B-cell and T-cell epitope-based vaccines. In this study, by harnessing immunoinformatics tools, we designed a multiple-epitope vaccine to protect against COVID-19. The candidate epitopes were designed from highly conserved regions of the SARS-CoV-2 spike (S) glycoprotein. The consensus amino acids sequence of ten SARS-CoV-2 variants including Gamma, Beta, Epsilon, Delta, Alpha, Kappa, Iota, Lambda, Mu, and Omicron was involved. Applying the multiple sequence alignment plugin and the antigenic prediction tools of Geneious prime 2021, ten predicted variants were identified and consensus S-protein sequences were used to predict the antigenic part. According to ElliPro analysis of S-protein B-cell prediction, we explored 22 continuous linear epitopes with high scores ranging from 0.879 to 0.522. First, we reported five promising epitopes: BE1 1115-1192, BE2 481-563, BE3 287-313, BE4 62-75, and BE5 112-131 with antigenicity scores of 0.879, 0.86, 0.813, 0.779, and 0.765, respectively, while only nine discontinuous epitopes scored between 0.971 and 0.511. Next, we identified 194 Major Histocompatibility Complex (MHC) - I and 156 MHC - II epitopes with antigenic characteristics. These spike-specific peptide-epitopes with characteristically high immunogenic and antigenic scores have the potential as a SARS-CoV-2 multiple-epitope peptide-based vaccination strategy. Nevertheless, further experimental investigations are needed to test for the vaccine efficacy and efficiency.

Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.

Introduction: Diabetes is a global disease, commonly complicated by neuropathy. The spinal cord reacts to diabetes by neuronal apoptosis, microglial activation, and astrocytosis, with a disturbance in neuronal and glial Nuclear factor erythroid 2-related factor/Heme oxygenase-1 (Nrf2/HO-1) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling. Curcumin, a bioactive natural substance, showed neuroprotective role in many diseases. However, its role in the treatment of the diabetic central neuropathy of spinal cord and the underlying mechanisms still need clarification. The present study tried to evaluate the role of curcumin in diabetes-induced central neuropathy of the spinal cord in rats. Methods: Twenty rats were divided into three groups; group 1: a negative control group; group 2: received streptozotocin (STZ) to induce type I diabetes, and group 3: received STZ + Curcumin (150 mg/kg/day) for eight weeks. The spinal cords were examined for histopathological changes, and immunohistochemical staining for Glia fibrillary acidic protein (GFAP); an astrocyte marker, Ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker, neuronal nuclear protein (NeuN); a neuronal marker, caspase-3; an apoptosis marker, Nrf2/HO-1, NF-kB, and oxidative stress markers were assessed. Results: Curcumin could improve spinal cord changes, suppress the expression of Iba1, GFAP, caspase-3, and NF-kB, and could increase the expression of NeuN and restore the Nrf2/HO-1 signaling. Discussion: Curcumin could suppress diabetic spinal cord central neuropathy, glial activation, and neuronal apoptosis with the regulation of Nrf2/HO-1 and NF-kB signaling.

Carbohydrate ligands-directed active tumor targeting of combinatorial chemotherapy/phototherapy-based nanomedicine: A review.

Phototherapies or light mediated therapies, including mutually photothermal and photodynamic therapy that encompass irradiation of the target organs with light, have been widely employed as minimally invasive approach associated with negligible drug resistance for eradicating multiple tumors with minimal hazards to normal organs. Despite all these advantages, many obstacles in phototherapy hinder progress toward clinical application. Therefore, researchers have developed nano-particulate delivery systems integrated with phototherapy and therapeutic cytotoxic drugs to overcome these obstacles and achieve maximum efficacy in cancer treatment. Active targeting ligands were integrated into their surfaces to improve the selectivity and tumor targeting ability, enabling easy binding and recognition by cellular receptors overexpressed on the tumor tissue compared to normal ones. This enhances intratumoral accumulation with minimal toxicity on the adjacent normal cells. Various active targeting ligands, including antibodies, aptamers, peptides, lactoferrin, folic acid and carbohydrates, have been explored for the targeted delivery of chemotherapy/phototherapy-based nanomedicine. Among these ligands, carbohydrates have been applied due to their unique features that ameliorate the bioadhesive, noncovalent conjugation to biological tissues. In this review, the up-to-date techniques of employing carbohydrates active targeting ligands will be highlighted concerning the surface modification of the nanoparticles for ameliorating the targeting ability of the chemo/phototherapy.

Modulation of immune responses to liposomal vaccines by intrastructural help.

The encapsulation of HIV-unrelated T helper peptides into liposomal vaccines presenting trimers of the HIV-1 envelope glycoprotein (Env) on the surface (T helper liposomes) may recruit heterologous T cells to provide help for Env-specific B cells. This mechanism called intrastructural help can modulate the HIV-specific humoral immune response. In this study, we used cationic T helper liposomes to induce intrastructural help effects in a small animal model. The liposomes were functionalized with Env trimers by a tag-free approach designed to enable a simplified GMP production. The pre-fusion conformation of the conjugated Env trimers was verified by immunogold electron microscopy (EM) imaging and flow cytometry. The liposomes induced strong activation of Env-specific B cells in vitro. In comparison to previously established anionic liposomes, cationic T helper liposomes were superior in CD4+ T cell activation after uptake by dendritic cells. Moreover, the T helper liposomes were able to target Env-specific B cells in secondary lymphoid organs after intramuscular injection. We also observed efficient T helper cell activation and proliferation in co-cultures with Env-specific B cells in the presence of cationic T helper liposomes. Mouse immunization experiments with cationic T helper liposomes further revealed a modulation of the Env-specific IgG subtype distribution and enhancement of the longevity of antibody responses by ovalbumin- and Hepatitis B (HBV)-specific T cell help. Thus, clinical evaluation of the concept of intrastructural help seems warranted.

Rare complication of open reduction and internal fixation of fracture distal radius: A case report of distal radioulnar synostosis.

Case: A 57-years old man who sustained left distal radius fracture. We performed distal radius ORIF. At follow up visit, he could not achieve any supination-pronation movements. Radiographs showed radioulnar synostosis. Four months later, we performed excision of synostosis with interposition of fat graft in the left forearm. A year later, the patient showed good forearm pronation and supination. Conclusion: This a rare case of radioulnar synostosis after ORIF distal radius fracture. Surgical intervention will help to improve the outcomes.

The hepatoprotective effects of n3-polyunsaturated fatty acids against non-alcoholic fatty liver disease in diabetic rats through the FOXO1/PPARα/GABARAPL1 signalling pathway.

AIM: We compared the efficacy of n3-polyunsaturated fatty acids (n3-PUFAs) and metformin in halting the progression of non-alcoholic fatty liver disease (NAFLD) developed in the milieu of insulin deficiency. MAIN METHODS: NAFLD was induced by a chronic high-fat diet (HFD) in male Sprague Dawley rats, rendered diabetic by a low dose streptozotocin (STZ). Diabetic rats were treated with n3-PUFAs (300 mg/kg/d) or metformin (150 mg/kg/d) for 8 weeks. Improvements in the NAFLD score and hepatic insulin resistance (IR) were addressed and correlated to changes in the hepatic expression of Forkhead box protein O1 (FOXO-1), microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) genes. Hepatic peroxisome proliferator-activated receptor alpha (PPAR-α), and B-cell lymphoma 2 (Bcl-2) protein expression was also assessed. KEY FINDINGS: Driven by insulin deficiency and HFD, the FOXO-1 gene along with its downstream targets, MAP1LC3B and GABARAPL1, were highly expressed in the liver tissue of the HFD/STZ group. Meanwhile, hepatic expression of PPAR-α and Bcl-2 was markedly decreased. These abnormalities coincided with a marked increase in the hepatic IR and NAFLD activity. Comparable to metformin, n3-PUFAs were able to rearrange hepatic PPAR-α and FOXO-1 expression in HFD/STZ rats, resulting in improved diabetic/steatotic liver phenotype. SIGNIFICANCE: Along with the enhancement of PPAR-α expression, inhibition of FoxO1/GABARAPL1/MAP1LC3B transcription is suggested as a core mechanism for the protective effects of n3-PUFAs on hepatic IR and NAFLD. Under conditions of insulin deficiency, n3-PUFAs retain their potential as a safe and promising approach for the control of NAFLD.

Surgical Fixation of Three- and Four-Part Proximal Humeral Fractures Using the Proximal Humeral Interlocking System Plate.

Introduction The management of proximal humeral fractures ranges greatly from conservative management to surgical treatment. For those fractures requiring surgical treatment, internal fixation is the primary method. The aim of internal fixation is to achieve rigid fracture fixation until union occurs, return of shoulder range of motion, and minimise intra-and postoperative complications. The aim of this study was to evaluate the results of the Proximal Humeral Interlocking System Plate (PHILOS) used for the treatment of three-and four-part proximal humeral fractures. Materials and methods This study included 30 patients with a mean age of 54 years (range 20-80 years). Results were checked post-operatively with standard radiographs and clinical evaluation according to the Constant-Murley shoulder score. All patients were followed up for 12 months. Results Union was achieved in all patients with a mean neck/shaft angle of 130° (range 108°-150°). The mean Constant-Murley score at the final follow-up was 82.28 (range 67-96) correlating with good results. No patients developed an intraoperative or postoperative vascular injury, wound complications, or avascular necrosis of the humeral head. Conclusion Our study has shown that the surgical treatment of three- and four-part proximal humeral fractures with the use of the PHILOS plate leads to a good functional outcome. It has also demonstrated the PHILOS plate and is an effective system for fracture stabilisation provided the correct surgical technique is used with awareness of potential hardware complications.

Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice.

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFß and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFß and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity.

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors.

Long-term use of Glucocorticoids produces skeletal muscle atrophy and microvascular rarefaction. Hydrogen sulfide (H2S) has a potential role in skeletal muscle regeneration. However, the mechanisms still need to be elucidated. This is the first study to explore the effect of Sodium hydrosulfide (NaHS) H2S donor, against Dexamethasone (Dex)-induced soleus muscle atrophy and microvascular rarefaction and on muscle endothelial progenitors and M2 macrophages. Rats received either; saline, Dex (0.6 mg/Kg/day), Dex + NaHS (5 mg/Kg/day), or Dex + Aminooxyacetic acid (AOAA), a blocker of H2S (10 mg/Kg/day) for two weeks. The soleus muscle was examined for contractile properties. mRNA expression for Myostatin, Mechano-growth factor (MGF) and NADPH oxidase (NOX4), HE staining, and immunohistochemical staining for caspase-3, CD34 (Endothelial progenitor marker), vascular endothelial growth factor (VEGF), CD31 (endothelial marker), and CD163 (M2 macrophage marker) was performed. NaHS could improve the contractile properties and decrease oxidative stress, muscle atrophy, and the expression of NOX4, caspase-3, Myostatin, VEGF, and CD31 and could increase the capillary density and expression of MGF with a significant increase in expression of CD34 and CD163 as compared to Dex group. However, AOAA worsened the studied parameters. Therefore, H2S can be a promising target to attenuate muscle atrophy and microvascular rarefaction.