High frequency neuronavigated repetitive transcranial magnetic stimulation in post-stroke shoulder pain: A double-blinded, randomized controlled study.

OBJECTIVE: This study aimed to determine the effect of 5Hz neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the affected primary motor cortex (M1) on pain, the effect of pain on activities of daily living, disability, mood, neurophysiological parameters and passive shoulder joint range of motion in patients with post-stroke shoulder pain. DESIGN: Twenty two patients were randomized into an experimental group (rTMS, n=7) who received daily rTMS 5Hz 1000 pulses, five times/week for three weeks (15 sessions) to the affected M1 and a control group (n=11) who received sham stimulation. Outcome measures were Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Disabilities of the arm, shoulder, and hand questionnaire (Quick DASH), Hospital Depression Anxiety Scale (HADS), joint range of motion (ROM) measurements, neurophysiological parameters. Selected outcome measures were performed before treatment (T0), after the 5th session (T1) of rTMS treatment, after the 10th session (T2), after the 15th session (T3), and four weeks after the end of the treatment (T4). In the analysis of the outcomes, within-group comparisons were performed by using the Wilcoxon or Friedman test and between-group comparisons were performed by using the Mann-Whitney U test. RESULTS: There was no statistically significant difference between and within groups in terms of change- and followup scores in the NRS measurements (p>0.05). BPI scale was found to be lower in rTMS group at T0 and T3 (p= 0.010). Quick-DASH scores at T4 were found to be significantly lower in rTMS group (p= 0.032). However, no difference was found within each group over time (p>0.05) and there was no statistical difference between the groups in terms of change scores (T3-T0 and T4-T0) (p>0.05) for BPI and Quick-DASH. In rTMS group, there was a statistically significant difference in shoulder external rotation at T3 compared to the baseline (T0) (p=0.039). However, the magnitude of external rotation change (T3-T0) with the treatment was comparable in the groups. No statistically significant change occurred in both treatment groups in other range of motion measurements. CONCLUSION: High frequency neuronavigated rTMS to the affected M1 did not show any significant beneficial effect on pain, activities of daily living, disability, anxiety and depression, neurophysiological measurements and passive ROM over sham stimulation.

Evaluation of YouTube videos as sources of information about complex regional pain syndrome.

Background: As the internet usage becomes easily accessible, the patients are more frequently searching about diseases and medical/non-medical treatments. Considering that complex regional pain syndrome (CRPS) is a debilitating disease, it is important to check the information that patients are accessing. Therefore, this study aimed to investigate the reliability, sufficiency, and accuracy of the YouTube videos about CRPS. Methods: This study is a descriptive research which is derived by searching videos using the keyword 'complex regional pain syndrome' on YouTube. Relevance-based sequencing was used to sort the videos. Sources and video parameters were documented. To evaluate the accuracy, reliability and content quality of the videos, Global Quality Score, Journal of American Medical Association Benchmark Criteria and Modified DISCERN Questionnaire scales were used. Results: A total of 167 videos were included in this study. The majority of the videos originated from USA (80.2%, n = 134). The median number of views was 639 and the viewing rate was 73.3. Most of the videos had partially sufficient data and the interaction index viewing rate parameters for videos with high content quality were greater than videos with low content quality (P = 0.010, P = 0.014). Conclusions: Our results showed that videos about CRPS on YouTube mostly had partially sufficient data and include intermediate-high quality contents. Moreover, high-content quality videos had higher viewing rates, interaction indexes, number of likes, longer durations, as well as better reliability and accuracy scores. Videos with high quality and reliable content are needed to reduce misinformation about CRPS.

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency.

NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are afflicted with life threatening recurrent microbial infections. Paradoxically, the spectrum of clinical manifestations includes severe inflammatory disorders. The mechanisms leading to autoinflammation in NEMO deficiency are currently unknown. Herein, we sought to investigate the underlying mechanisms of clinical autoinflammatory manifestations in a 12-years old male NEMO deficiency (EDA-ID, OMIM #300,291) patient by comparing the immune profile of the patient before and after hematopoietic stem cell transplantation (HSCT). Response to NF-kB activators were measured by cytokine ELISA. Neutrophil and low-density granulocyte (LDG) populations were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) transcriptome before and after HSCT and transcriptome of sorted normal-density neutrophils and LDGs were determined using the NanoString nCounter gene expression panels. ISG15 expression and protein ISGylation was based on Immunoblotting. Consistent with the immune deficiency, PBMCs of the patient were unresponsive to toll-like and T cell receptor-activators. Paradoxically, LDGs comprised 35% of patient PBMCs and elevated expression of genes such as MMP9, LTF, and LCN2 in the granulocytic lineage, high levels of IP-10 in the patient's plasma, spontaneous ISG15 expression and protein ISGylation indicative of a spontaneous type I interferon (IFN) signature were observed, all of which normalized after HSCT. Collectively, our results suggest that type I IFN signature observed in the patient, dysregulated LDGs and spontaneously activated neutrophils, potentially contribute to tissue damage in NEMO deficiency.

Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection.

BACKGROUND: Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2. METHODS: VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. RESULTS: Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals. CONCLUSION: These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.

Comparison of Real-Time Speech Magnetic Resonance Imagings With Perceptual Speech Analysis in Evaluation Velopharyngeal Sphincter Function.

ABSTRACT: Identifying substantial data and their normative values related to velopharyngeal structures in cleft palate patients may have clinical significance, in order to selection of surgical intervention and prediction of postsurgical outcomes. Previous studies are lack of referring certain anatomic locations or distances that may have affect on speech intelligibility, especially in dynamic state. The aim of this study is to investigate effectiveness of magnetic resonance imagings on the velopharyngeal sphincter function and the correlation with speech intelligibility after functional cleft palate repair. Seventeen patients with repaired cleft palate by single surgeon were enrolled in this study.Quantitative velopharyngeal measures from the oblique coronal plane and midsagittal plane in static and dynamic positions were collected. Patients' speech intelligibility was evaluated by using Pittsburgh Weighted Speech Scale and nasalance score was also measured. Correlation analysis methods were used for evaluating relation between MRI gathered measurements and speech intelligibility scores for determiningconsequential data.Our study shows that the velar knee-posterior pharyngeal wall distance measurement while explosive sound production is the most related data with speech intelligibility. Although future works with more sample number is needed, according to current study the authors think magnetic resonance imagings is a very helpful method in providing reliable information.

Comparison of Ischemic Preconditioning and Systemic Piracetam for Prevention of Ischemia-Reperfusion Injury in Musculocutaneous Flaps.

BACKGROUND: Ischemia-reperfusion injury plays an important role in flap failure. Ischemic preconditioning technique is the only proven method for preventing ischemia-reperfusion injury, but it is not used widely in daily practice because of difficulties such as prolonging the operation time, need for surgical experience, and increasing the risk of complications. This study has been performed with the assumption that piracetam may be a simple and inexpensive alternative to the preconditioning technique due to its antioxidant, antiaggregant, rheological, anti-inflammatory, antiapoptotic, cytoprotective, and immune modulating effects. METHODS: Thirty-two rats were divided into four groups and latissimus dorsi musculocutaneous flaps were raised. No extra procedure was applied, and no treatment was given to the control group. Four hours of ischemia was created by clamping the thoracodorsal pedicle in the second group. The animals in the third group were treated with 10 minutes of ischemia and reperfusion periods as a preconditioning procedure before the 4 hours of ischemia. Animals in the fourth group received systemic piracetam 30 minutes before and 6 days after reperfusion. Nitric oxide and myeloperoxidase levels in serum and tissue, acute inflammatory cell response, and vascular proliferation in tissue were examined at the postoperative 24th hour and 10th day. RESULTS: Myeloperoxidase activity in both preconditioning and piracetam groups, was significantly lower than the ischemia-reperfusion group. Acute inflammatory cell response was similarly decreased in both preconditioning and piracetam groups compared with ischemia-reperfusion group. Tissue measurements of nitric oxide were also significantly higher in both preconditioning and piracetam groups than in the ischemia-reperfusion group. However, vascular proliferation increased in the preconditioning group, while it did not show any significant change in the piracetam group. CONCLUSION: This study shows that systemic piracetam treatment provides protection against ischemia-reperfusion injury in musculocutaneous flaps and can offer a simple and inexpensive alternative to the preconditioning technique.

Comparison of ischemic preconditioning and BotulinumA Toxin injection for the prevention of ischemia-reperfusion injury in musculocutaneous flaps

Background/aim: The aim of the study was to evaluate the protective effect of Botulinum A toxin injection against ischemia-reperfusion injury. Materials and methods: Thirty-two Sprague-Dawley rats were divided into: control, ischemia-reperfusion, ischemic preconditioning, and botulinum groups. In all groups the musculocutaneous pedicle flap was occluded for 4 h, and then reperfused to induce ischemia-reperfusion injury. Serum and tissue myeloperoxidase (MPO) and nitric oxide (NO) levels were measured at 24 h and at 10 days. Results: Tissue MPO levels did not differ significantly between the ischemic preconditioning and botulinum groups at 24 h but was significantly lower in the botulinum group at 10 days. Tissue NO levels were significantly higher in the ischemic preconditioning group compared to the botulinum group at 24 h and at 10 days. Serum MPO showed no significant difference between these two groups at 24 h but was significantly lower in the ischemic preconditioning group compared to the botulinum group at 10 days. Serum NO levels were not significantly different at 24 h but significantly higher in the botulinum group at 10 days. Conclusion: Findings show that botulinum has a protective effect against the ischemia-reperfusion injury via increased NO and decreased MPO levels in tissue. Based on tissue NO levels, ischemic preconditioning was significantly higher than botulinum.

The New Anatomical Classification System for Orbital Exenteration Defect.

BACKGROUND: The unique anatomy of the orbita and the different behavior of each malignant tumor cause us to perform the various types of orbital exenteration that yields to varying defect each of which has own specific demands in terms of the reconstruction. Current classification of orbital exenteration defects seems not to be adequate to provide detailed description. This study reviews 50 exenteration defects to offer a more effective anatomical classification system. METHODS: Over a 15 years period, 50 orbital exenteration defects in 47 patients were reconstructed. Defects were categorized according to the resected orbital wall, dura, and ethmoid resection. If the maxillectomy was performed, A or B was added to define the type of maxillectomy as partial (intact palate) or total maxillectomy, respectively. According to these criteria, 4 types of defect patterns were determined including Type 0 (n = 5) with intact orbital wall, Type I (n = 9) with sino-orbital fistula, Type II (n = 4) with crania-orbital fistula with intact dura, Type III (n = 6) with crania-orbital fistula associated with dura defect, and Type IV (n = 8) with cranio-nasal-orbital fistula. There were 12 partial (A) and 6 total maxillectomy (B) defects along with the orbital exenteration. RESULTS: There was no major complication except one. The minor wound-healing problems occurred in 7 patients. Nine patients (19%) used prosthesis. Twenty-two (46.8%) patients chose a patch to cover the area. The remaining 16 patients were not able to use any type of prosthesis because of the reconstruction methods. CONCLUSION: The authors believe that the authors' anatomical classification system provides more precise description of the defect which eventually enhances the success rate of both reconstruction and resection.

Extended locoregional use of intercostal artery perforator propeller flaps.

Besides conventional flaps, intercostal artery perforator flaps have been reported to cover trunk defects. In this report the use of anterior intercostal artery perforator (AICAP) flap, lateral intercostal artery perforator (LICAP) flap and dorsal intercostal artery perforator (DICAP) flap for thoracic, abdominal, cervical, lumbar and sacral defects with larger dimensions and extended indications beyond the reported literature were reevaluated. Thirty-nine patients underwent surgery between August 2012 and August 2014. The age of the patients ranged between 16 and 79 with a mean of 49 years. The distribution of defects were as follows; 12 thoracic, 8 parascapular, 3 cervical, 8 abdominal, 4 sacral and 4 lumbar. AICAP, LICAP and DICAP flaps were used for reconstruction. Fifty-two ICAP flaps were performed on 39 patients. Flap dimensions ranged between 6 × 9 cm and 14 × 35 cm. Twenty-six patients had single flap coverage and 13 patients had double flap coverage. Forty-six flaps have been transferred as propeller flaps and 6 flaps have been transferred as perforator plus flap. Forty flaps (75%) went through transient venous congestion. In one DICAP flap, 30% of flap was lost. No infection, hematoma or seroma were observed in any patient. Follow-up period ranged between 3 and 32 months with a mean of 9 months. The ICAP flaps provide reliable and versatile options in reconstructive surgery and can be used for challenging defects in trunk.

Locoregional use of lateral thoracic artery perforator flap as a propeller flap.

Although thoracodorsal system is a fundamental source of various flaps, lateral thoracic region has not been a popular flap donor area. There is limited data on the use of lateral intercostal artery perforator flap and lateral thoracic artery perforator flap. In this case series, lateral thoracic artery perforator flap has been used in locoregional (axilla, pectoral region, and arm) reconstruction as an island or propeller flap.Eighteen patients have been operated on between September 2010 and January 2013. The age of the patients ranged between 16 and 68 years with a median of 38 years. A thorough chart review has been performed with preoperative and postoperative photographs. Duration of hospitalization, complication rate and long term results have been documented.Nine patients had severe burn contracture of axilla, 7 patients had axillary hidradenitis suppurativa, 1 patient had giant neurofibroma of arm, and 1 patient had malignant peripheral nerve sheath tumor of pectoral area. Seventeen flaps survived totally, and in 1 flap, distal superficial slough of skin has been observed. No recurrence in hidradenitis or peripheral nerve sheath tumor has been observed. Donor site scar is well hidden in anatomical position. The range of motion of affected extremities returned to normal after reconstruction.Lateral thoracic area provides a reliable flap option with a wide arc of rotation when lateral thoracic artery perforators are used.

Biogenic volatile organic compound (BVOC) emissions from forested areas in Turkey: determination of specific emission rates for thirty-one tree species.

Normalized biogenic volatile organic compound (BVOC) emission rates for thirty one tree species that cover the 98% of national forested areas in Turkey were determined. Field samplings were performed at fourteen different forested areas in Turkey using a specific dynamic enclosure system. The selected branches of tree species were enclosed in a chamber consisted of a transparent Nalofan bag. The air-flows were sampled from both inlet and outlet of the chamber by Tenax-filled sorbent tubes during photosynthesis of trees under the presence of sunlight. Several environmental parameters (temperature, humidity, photosynthetically active radiation-PAR, and CO2) were continuously monitored inside and outside the enclosure chamber during the samplings. Collected samples were analyzed using a gas chromatography mass spectrometry (GC/MS) system equipped with a thermal desorber (TD). Sixty five BVOCs classified in five major groups (isoprene, monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, and other oxygenated compounds) were analyzed. Emission rates were determined by normalization to standard conditions (1000 µmol/m(2)s PAR and 30 °C temperature for isoprene and 30 °C temperature for the remaining compounds). In agreement with the literature, isoprene was mostly emitted by broad-leaved trees while coniferous species mainly emitted monoterpenes. Several tree species such as Sweet Chestnut, Silver Lime, and European Alder had higher monoterpene emissions although they are broad-leaved species. High isoprene emissions were also observed for a few coniferous species such as Nordmann Fir and Oriental Spruce. The highest normalized total BVOC emission rate of 27.1 µg/gh was observed for Oriental Plane while South European Flowering Ash was the weakest BVOC emitter with a total normalized emission rate of 0.031 µg/gh. Monoterpene emissions of broad-leaved species mainly consisted of sabinene, limonene and trans-beta-ocimene, while alpha-pinene, beta-pinene and beta-myrcene were generally emitted by coniferous species. Oxygenated compounds were the third most prominent BVOC group and sesquiterpenes had slightly lower contributions.

Psychiatric assessment of children with nonsyndromic cleft lip and palate.

OBJECTIVE: The aim of the study was to determine whether children with nonsyndromic cleft lip and palate (NSCLP) are more likely to be diagnosed with psychiatric disorders and whether cleft-related factors are related to psychopathology. METHOD: Twenty children from 6 to 16 years of age with NSCLP, attending the Plastic, Reconstructive and Aesthetic Surgery Department of Cerrahpasa Medical Faculty between January and October 2010, were included as the case group. Forty healthy children who were matched on age and sex with the case group served as controls. Children were assessed by psychiatric interviews and scales. RESULTS: Social anxiety disorder (SAD) (P=.003) and major depressive disorder (MDD) (P=.010) were more prevalent in children with NSCLP. The severity of dentofacial (P=.035) and cleft lip nose deformities (P=.002), appearance and competence of the lip (P=.008), dental alignment (P=.002), feeding (P=.044) and articulation problems (P<.001) were associated with clinical global functioning. CONCLUSIONS: Children with NSCLP are at risk of developing psychopathology, especially SAD and MDD. The above cleft-related factors and articulation problems may be the target of interventions to prevent and treat psychiatric disorders in these children.

Demonstration of circulation haemodynamics in random pattern thinned skin flap (an experimental study).

BACKGROUND: Clinical applications and indications of the thin skin flap have been widely documented but its circulation haemodynamics are still controversial. An experiment was conducted on pigs to show the survival and circulation haemodynamics of random pattern thinned skin flap. METHODS: Group I: Random pattern standard skin flaps; 5 x 5 cm (n=20 flaps), and 5 x 10 cm (n=20 flaps). Group II: Random pattern thin skin flaps; 5 x 5 cm (n=20 flaps), and 5 x 10 cm (n=20 flaps). Group III: Random pattern thin skin flaps with silicone sheet underneath; 5 x 5 cm (n=20 flaps), and 5 x 10 cm (n=20 flaps). RESULTS: The mean surviving skin area of the 5 x 10 cm flaps was 95.5% in Group I, 64.9% in Group II, and 33.67% in Group III. A statistically significant difference (P<0.05, ANOVA) was found between the groups. The mean surviving skin area of the 5 x 5 cm flaps was 100% in Groups I and II, and 68.2% in Group III. A statistically significant difference (P<0.05, ANOVA) was also found between Groups I and III, and Groups II and III. In microangiographical studies, the distribution of subcutaneous plexuses was clearly visible in Group I. In Group II the subdermal vascular plexus was observed less frequently and was thinner, particularly on the distal part of the flaps. In Group III dilatation of the subdermal vascular plexus was evident, particularly on the proximal section of the flaps. In the technetium-99m-labelled microspheres uptake of the 5 x 10 cm flaps, there was no statistically significant difference between the first segments in Groups I and II, Groups II and III (P>0.05, ANOVA). A significant difference was found between the second segments in Groups I and III (P<0.05, ANOVA). CONCLUSION: The results obtained in this study show that the effect of subdermal vascular plexus in the survival of the random pattern thinned skin flaps is supported by flap bed osmosis and plasma imbibition.

Sclerotherapy to a large cervicofacial vascular malformation: a case report with 24 years' follow-up.

BACKGROUND: Large craniofacial venous malformations frequently cause significant cosmetic and functional problems. Treatment of the lesions early in life helps to avoid these problems. We present a case of a large cervicofacial venous malformation. METHODS: The patient was treated with a 5% benzyl alcohol solution of sodium morrhuate. The treatment was begun when the patient was 3 months of age, with a total of 23 injections. RESULTS: The lesion had completely disappeared by age 10. No major complications were observed except a superficial tissue loss on the temporal region. It was healed by conservative treatment. There were no recurrences during the 14-year follow-up. CONCLUSIONS: It is difficult to conclude that this type of treatment is the best choice for patients with venous malformation on the basis of a single case. However, intralesional sclerotherapy should be kept in mind as a saving treatment option in cases of large venous malformations in anatomic regions that present challenges to both the surgeon and the patient. Intralesional sclerotherapy can be performed without serious complications if the sclerosing agent is selected and injected cautiously.