Diabetes Therapy

Differential Effect of Hypoalbuminemia on Hypoglycemia on Type 2 Diabetes Patients Treated with Insulin Glargine 300 U/ml and Insulin Degludec Abstract Introduction Hypoglycemia resulting from insulin therapy for treatment of diabetes increases the risk of adverse cardiovascular events. Determining biomarkers that provide accurate estimation of hypoglycemia risk may allow for more accurate patient management and care. The purpose of this study was to determine the cutoff value of serum albumin (s-alb) that increases the risk of hypoglycemia in patients treated with insulin degludec. Methods This study used a crossover design and randomized 30 patients admitted for glycemic control to compare differences between insulin glargine 300 U/ml (Gla300) and degludec treatments. Results The cutoff value of s-alb associated with 24-h hypoglycemia and nocturnal hypoglycemia in patients treated with degludec was 3.8 g/dl. In patients with s-alb levels < 3.8 g/dl, mean percentages of time with hypoglycemia, clinically important hypoglycemia, and nocturnal hypoglycemia were significantly lower in those treated with Gla300 compared with patients treated with degludec. Conclusion This study identified a cutoff value for s-alb levels that indicates risk of hypoglycemia in patients treated with degludec. Monitoring s-alb levels in patients treated with degludec will help to mitigate the risk of hypoglycemia. Trial Registration University Hospital Medical Information Network (UMIN 000031044).

Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation Abstract Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18–26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.

American Diabetes Association 2019 Conference Podcast With the Editor-in-Chief: What Are the Outcomes from ADA This Year and What Are the Future Developments in Diabetes? Podcast recording of Fernando Ovalle live from the ADA 2019 conference in San Francisco (MP4 177883 kb)

Correction to: Management of Patients with Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide, Exenatide ER, Liraglutide and Lixisenatide: A Cost-Effectiveness Analysis in the Danish Setting In the original publication, Figs. 3 and 5 and the final sentence in the final paragraph of Results/Sensitivity Analyses were incorrectly published. The corrected statement and the figures are given below.

Clinical Efficacy and Parameters Affecting the Response to Dulaglutide Treatment in Patients with Type 2 Diabetes: A Retrospective, Real-World Data Study Abstract Introduction This study aimed to investigate the efficacy and clinical factors affecting the glycemic response to dulaglutide in type 2 diabetes (T2D) in a real-world clinical setting. Methods We conducted a retrospective study of 234 patients at the Asan Medical Center, Republic of Korea, who had T2D and initiated dulaglutide from June 2016 to December 2017. The primary outcome was the change in glycated hemoglobin (HbA1c) concentration between baseline and 6 months after the initiation of therapy. Multivariate regression analysis was used to determine the clinical parameters contributing to a superior glycemic response to dulaglutide. Results The mean age of the patients was 53, and 50% were male. Their mean baseline HbA1c, body mass index and duration of diabetes were 8.8%, 27.6 kg/m2 and 10.2 years, respectively. The change in HbA1c between baseline and 6 months was − 0.92% (95% CI: − 1.1% to − 0.74%, p < 0.001). The reduction in body weight over the same period was −2.1 kg (95% CI: − 2.9 to − 1.3 kg, p < 0.001). Using multivariate regression analysis, baseline HbA1c was found to be a significant predictor of superior glycemic response to dulaglutide. Conclusion The use of dulaglutide was associated with a significant reduction in HbA1c and body weight over a 6-month period in a real-world clinical setting. T2D patients with higher baseline HbA1c concentrations were more likely to demonstrate good clinical responses to dulaglutide.

Lower Renal Threshold for Glucose Reabsorption in Type 1 Diabetes Mellitus (T1DM) May Explain the Smaller Contribution of SGLT2 Inhibitors to the Improvement of Plasma Glucose Control Compared with T2DM Abstract Introduction Previously, we reported that the renal threshold for glucose reabsorption can be measured as the lowest plasma glucose level that correlates with the first detectable appearance of urine glucose. These data revealed significant variations among patients with type 2 diabetes mellitus (T2DM), and there was a significant negative correlation between the renal threshold for glucose reabsorption and HbA1c levels following treatment with the sodium-glucose co-transporter 2 (SGLT2) inhibitor ipragliflozin. Recently approved SGLT inhibitors may not show the same efficacy in patients with T1DM as in those with T2DM unless the renal threshold for glucose reabsorption shows similar levels between the two groups. SGLT2 inhibitors improve plasma glucose control in patients with T2DM by reducing glucose reabsorption via the epithelial cells of the proximal tubule. Methods The renal threshold for glucose reabsorption was defined as the minimum blood glucose concentration that results in the presence of measurable glycosuria in at least 12 measurements. Results The renal threshold for glucose reabsorption in patients with T2DM [n = 64; 201.8 ± 33.6 (range 121–268) mg/dL] was significantly higher than that in patients with T1DM [n = 33; 171.0 ± 33.0 (range 76–259) mg/dL; p = 0.00022]. Conclusion The renal threshold for glucose reabsorption in patients with T1DM was near the normal range and significantly lower than that in patients with T2DM. The efficacy of the SGLT2 inhibitor was better in patients with a higher renal threshold for glucose reabsorption. Thus, these results indicate that it is advisable to estimate the renal threshold for glucose reabsorption prior to initiating SGLT2 inhibitor therapy in patients with T1DM.

Effect of Intravitreal Anti-Vascular Growth Factor Agents With or Without Macular Photocoagulation on Diabetic Macular Edema: A Systematic Review and Meta-Analysis Abstract Introduction Diabetes is a common cause of new sight loss in populations world-wide, and diabetic macular edema (DME) is a major cause of visual deficits in the diabetic populations of developed countries. We have performed a meta-analysis to evaluate whether combined treatment with anti-vascular endothelial growth factor (VEGF) injections and macular photocoagulation (MPC) is more efficacious than primary monotherapy with anti-VEGF injections in patients with DME. Methods We systematically searched the PubMed and Web of Science databases for studies providing sufficient information for a comparison of pre- and post-treatment of central macular thickness (CMT) and best-corrected visual acuity (BCVA) between two groups of patients with DME given interventional therapies (monotherapy with an anti-VEGF agent vs. combination therapy with an anti-VEGF agent and MPC) before January 2019. A meta-analysis was performed to summarize the results of the studies included in the systematic review. Results The results of our meta-analysis indicated that post-treatment CMT was significantly lower at 3 months in DME patients receiving combination therapy with bevacizumab, a humanized anti-VEGF antibody, and MPC than in those receiving monotherapy with bevacizumab. The results also showed that post-treatment CMT was lower in DME patients given ranibizumab, an anti-VEGF agent, in combination with MPC at 6, 9 and 12 months than in those treated with ranibizumab alone. However, no significant differences were found in post-treatment BCVA at 1, 3, 6, 9 and 12 months between DME patients receiving combination therapy with an anti-VEGF agent (bevacizumab or ranibizumab) and MPC and those receiving monotherapy with an anti-VEGF agent. Conclusion In conclusion, the results of our meta-analysis demonstrate a transiently synergistic effect of MPC on CMT when this treatment is combined with anti-VEGF agents, whereas no similar synergistic effect could be detected on the BCVA. A relatively longer follow-up was essential to be able to evaluate the long-term existence of this synergistic effect.

Short-Term Versus Long-Term Adverse Cardiovascular Outcomes Post Percutaneous Coronary Intervention in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Simple Meta-Analysis Abstract Introduction Type 2 diabetes mellitus (T2DM) is a major health issue, especially in patients with coexisting coronary artery disease (CAD). Patients with insulin-treated T2DM (ITDM) have worse outcomes than those with non-insulin-treated T2DM. Very few studies have compared short-term to long-term adverse cardiovascular outcomes following percutaneous coronary intervention (PCI) in patients on insulin therapy. Therefore, in this meta-analysis, we systematically compared short-term to long-term adverse cardiovascular outcomes in a population of patients with ITDM following PCI. Methods We searched for English-language publications focusing on PCI in patients with ITDM using specific search terms/phrases. All the participants accepted for inclusion in this meta-analysis were treated with a drug-eluting stent. Post-intervention adverse cardiovascular outcomes observed during short-term and long-term follow-up periods were assessed and compared. Statistical analysis was carried out using the popular RevMan 5.3 software. Odd ratios (OR) with 95% confidence intervals (CI) were calculated. Results Six studies comprising 1568 participants with ITDM in total were included in this simple meta-analysis. Patient enrollment periods varied but enrollment occurred during the years 1993–2012. When a fixed-effects statistical model was used, post-PCI adverse cardiovascular outcomes—such as major adverse cardiac events (MACEs) (OR 3.33, 95% CI 2.64–4.21; P = 0.00001), all-cause mortality (OR 5.73, 95% CI 3.37–9.73; P = 0.00001), myocardial infarction (MI) (OR 1.47, 95% CI 1.05–2.07; P = 0.02), and repeated revascularization (OR 4.78, 95% CI 3.29–6.94; P = 0.00001)—were found to be significantly more likely during the long-term follow-up period. A similar result was observed with a random-effects statistical model. Conclusion Adverse cardiovascular outcomes post PCI were significantly more likely during the long-term follow-up period than during the short-term follow-up period in these patients with T2DM on insulin therapy. This hypothesis requires confirmation via new comparative trials that consider short-term and long-term follow-up periods.

Effects of Diabetes Numeracy on Glycemic Control and Diabetes Self-Management Behaviors in Patients on Insulin Pump Therapy Abstract Introduction Diabetes numeracy (DN) skills are crucial in patients on insulin pump therapy. Little evidence exists regarding DN in this patient population. Methods This exploratory, observational, cross-sectional study assessed the DN levels of patients on insulin pump therapy and potential relationships with glycemic control and self-management behaviors. Seventy-two patients on insulin pump therapy were recruited from one specialty endocrinology clinic. Subjects completed validated tools to measure DN [Diabetes Numeracy Test (DNT-15)] and self-management behaviors [Diabetes Self-Management Questionnaire (DSMQ)]. A general diabetes questionnaire assessed socioeconomic information and self-efficacy. Additional self-management behaviors and glycemic control data were collected from patients' medical records. Patients were categorized into two groups based on DNT-15 scores to explore potential relationships between DN scores and patient characteristics, glycemic control, and self-management behaviors. Results Average age was 52 ± 15 years, glycosylated hemoglobin (A1C) was 7.7% ± 1.2% (61 mmol/mol), duration of diabetes was 28 ± 15 years, and duration of pump use was 3.4 ± 1.3 years. The average DNT-15 score was 87.5% ± 18%. Forty-three participants (60%) scored ≥ 90% and 29 participants (40%) scored < 90%. Eighteen percent were unable to calculate the carbohydrate content from a nutrition label. Participants with lower DNT-15 scores had higher A1C levels (8.0% vs. 7.5%, p = 0.04), were older (58.3 vs. 47.7, p = 0.003), were more likely to describe their diabetes self-care as poor (p = 0.04), and were less confident in using their pump features (p = 0.02) than those with higher DNT-15 scores. Conclusion Many patients on insulin pump therapy have deficiencies with DN which may be associated with older age and higher A1C levels.

Retrospective Database Analysis Evaluating the Clinical Outcomes of Changing Treatment of People with Type 2 Diabetes Mellitus (T2DM) from Other DPP-4 Inhibitor Therapy to Alogliptin in a Primary Care Setting Abstract Introduction Although some differences between individual dipeptidyl peptidase-4 (DPP-4) inhibitors may exist, the National Institute for Health and Clinical Excellence (NICE) have recommended that 'prescribers should be encouraged to select the individual DPP-4 inhibitor with the lowest acquisition cost available to them, where all other factors are equal'. We aimed to determine whether or not 'within class' switching to alogliptin, the DPP-4 inhibitor with lowest acquisition cost, is a clinically appropriate strategy. Methods This study evaluated people with type 2 diabetes taking DPP-4 inhibitor therapy in addition to at least one other diabetes therapy. Primary care records were reviewed from six clinical commissioning groups (CCGs). For people who had been switched from other DPP-4 inhibitors to alogliptin, an assessment of the impact of switch on both absolute haemoglobin A1c (HbA1c) levels and on HbA1c trajectory was undertaken. Persistence on alogliptin and the need for therapy intensification was also assessed. Results Overall, 865 people with diabetes met the eligibility criteria for the study. There was no significant difference between pre- and post-switch mean HbA1c level [8.44% (SD 1.52%) vs 8.42% (1.62%), p = 0.6]. Similarly, for patients where there was sufficient data to assess the impact of switching on HbA1c trajectory (n = 319) minimal impact was identified (actual HbA1c at 3 months 8.33% vs projected 8.31%). The majority of people with diabetes (80.76%) remained on alogliptin treatment at 6 months and only 4.54% required additional diabetes therapies. Switching to alogliptin resulted in a median saving of £7.24 per patient-month. Conclusion Switching United Kingdom (UK) primary care patients from other DPP-4 inhibitors to alogliptin did not result in a statistically significant or clinically meaningful change in HbA1c level and few required the addition of further diabetes therapies, suggesting that therapy change or intensification was not considered necessary in most patients who were switched to alogliptin. Trial Registration ENCePP clinical trial registration number EUPAS29153. Funding Takeda UK Ltd.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com

Surgery

Complex Liver Injury—a Quagmire to a Trauma Surgeon Abstract Non-operative management has become a norm in patients with liver trauma and operative management is guided by hemodynamic status. Introduction of haemodynamic status. Introduction of contrast enhanced computed tomography (CECT) abdomen has made NOM possible by helping in exclusion of other injuries and identification of vascular injuries. Haemodynamic instability is now considered as an only absolute indication for operative intervention in liver injuries. However, liver trauma is associated with a large number of complications in the form of perihepatic abscess, hepatic necrosis, bile leak, etc. Patient's undergoing operative intervention for liver trauma are more at risk for these complications. As such regular dynamic assessment is required for early identification and management of these complications. We present a case of a complex liver injury in a 27-year-old male who underwent operative intervention for liver trauma and had a varied number of liver trauma associated complications, with enterohepatic fistula as one of the rarest associated complications.

Elevation of Thin Pudendal Artery Flap Using Fat Thickness Data in Vulvovaginal Reconstruction Abstract Majority of defects after excision of vulvovaginal skin cancers is shallow in depth. A thin flap is thus suitable for pudendal defects. To create a thin pudendal artery flap, the relationship between fat thickness and age or body mass index (BMI) was examined. A total of 12 flaps in 7 cases were enrolled. In the initial 3 cases, five flaps were elevated in the subfascial plane of the gluteus maximus muscle based on the conventional method. In the 4th case with thick adipose tissue, the flap was elevated in the plane just below Camper's fascia (CF). We then adopted this modified flap elevation method in 7 flaps of the 4th to 7th cases. By using computed tomography, we evaluated the perineal fat thickness (PFT) and gluteal fat thickness (GFT) to determine the thickness of the flap. All flaps survived completely. In all flaps prepared with the modified method, debulking was not required. The mean PFT (34.4 ± 2.8 mm) of the patients less than 70 years of age was significantly higher than that of patients of 70 years or more (21.0 ± 3.5 mm). The mean GFT (18.4 ± 1.1 mm) of the patients with BMI ≥ 25 was significantly higher than that of patients with BMI < 25 (11.8 ± 1.2 mm). To create a thin pudendal artery flap, the method of elevating the flap in the plane just deep to CF should be adopted, especially in patients less than 70 years of age or with BMI ≥ 25.

Posterior Epidural Migration of a Lumber Disc Fragment Causing Cauda Equina: a Case Report and Literature Review Abstract Cauda equina syndrome manifests as bilateral leg pain and sensory disturbances in the perianal region. In this article, authors describe patient with posterior epidural disc migration of a lumber disc fragment causing cauda equina syndrome and provide review of the literature.

Sialolipoma of Parotid Gland: a Lesser Known Entity Abstract Around 51 cases of sialolipoma of the salivary gland have been reported worldwide as per the literature reviewed. Majority of cases (n = 25) arise from the parotid gland (51.4%) clinically behaving like pleomorphic adenoma with very less incidence of facial nerve entrapment (14%). Sialolipoma is a rare neoplasm of the salivary glands, described as a distinct entity by Nagao et al. in 2001. Lipomatous neoplasms of the parotid gland are rare tumours accounting 0.6 to 4.4% of all parotid neoplasms with most series reporting an incidence of 1%. It is extremely rare in females, being 10 times more common in males, and the most common age of presentation is the fifth to sixth decade. Numerous histological variants of salivary gland lipoma have been described. Sialolipoma is a rare variant having proliferation of mature adipocytes with secondary entrapment of the normal salivary gland element. We report a rare case of sialolipoma in the left parotid of a 49-year-old woman presented to General Surgery Department who was treated with superficial parotidectomy.

Residents Feedback on Faculty and Working Environment: the Urology Training Program in India Abstract The purpose of our study was to know the residents' feedback regarding urology residency in India. Such information is presently scarce. The feedback included evaluating domains like faculty participation in academic activities and resident-friendly learning workplace. It also asked residents what change they wished to see in faculty and an overall rating of their residency program. An online survey was conducted using SurveyMonkey® platform. E-mails with an online link to survey were sent to 1469 associate members of Urological Society of India. There were 12 queries. The responses between residents in M.Ch. and D.N.B. programs, the two officially recognized teaching programs in India, were also compared. Seventy-eight current residents or those who completed residency within 1 year finished the survey. The unfavorable responses towards faculty involvement in academic activities, teaching and creating a friendly work place varied from 20 to 30% for most questions. When asked about what change in faculty the residents wanted, 45.5% reported "better involvement in teaching" followed by creation of a friendly workplace environment (37%). The overall mean satisfaction rating with the program on a scale of 0–100 was 66.04 ± 22.51. The responses of residents from the M.Ch. and D.N.B. programs were similar (p > 0.05). Our results provide some insight on the resident's perspective of their training/teaching programs in Indian urology centers. Although, a comprehensive validated questionnaire was not used but our observations can be used to improve the learning of students doing residency in urology.

Quality Improvement in Laparoscopic Donor Nephrectomy by Self-Imposed Proctored Preceptorship Model Abstract Initiation of an advanced laparoscopic surgery program requires skill and proper training. Despite description of multiple surgical training modules, an ideal method for training of surgeons for advanced laparoscopic procedures is lacking. We propose an abbreviated self-imposed proctored preceptorship training model as the optimum training method for training skilled laparoscopic surgeons in advanced laparoscopic procedures like laparoscopic donor nephrectomy. The laparoscopic donor nephrectomy program was started at the Institute using preceptorship-proctorship model. One hundred left laparoscopic donor nephrectomies were performed over the course of 2 years. Outcomes in terms of performance related (Surgeon) outcomes in the form of learning curve and patient outcomes in terms of donor outcomes and recipient results and were studied. Learning curve was calculated using the moving average method and calculation of mean operative time of every five consecutive cases. Mean operative time for laparoscopic donor nephrectomy was 108.1 ± 26.5 min, the warm ischemia time averaged at 3.5 ± 1.3 min and the mean blood loss was 130.1 ± 54.9 ml. Moving average analysis revealed that approximately 20 LDN cases were needed to complete the learning phase. According to the mean operative time of every five consecutive cases, learning phase of LDN was completed between 26 and 30 cases. We believe that the abbreviated self-imposed proctored preceptorship model of training is an optimum model for starting a new advanced laparoscopic surgery program and can help surgeons to overcome the initial learning curve.

Giant Pleomorphic Liposarcoma of the Chest Wall in an Octogenarian Woman Abstract Liposarcomas usually originate in the extremities and retroperitoneum. Primary malignant soft-tissue sarcoma of the chest is a rare entity. We described a case of an 80-year-old woman with a large and painless mass on right posterior chest wall.

Bilateral Fungating Metastatic Breast Cancer: Case Report Abstract Breast cancer is the most common cancer among females; while incidence of breast cancer increase with age, yet screening programs in most countries stop inviting patients beyond the age of 70 years. In spite all the efforts and resources geared for early detection of breast cancer, fungating locally advanced breast cancer remains a clinical challenge with the majority of patients either have metastatic disease at presentation or develop distant metastases despite appropriate therapy, leading to poor outcome. We are presenting a case of a patient who presented with locally advanced, fungating, metastatic breast cancer in spite of a very efficient screening program.

A Bibliometric Analysis of Pectoral Nerve Blocks Abstract Pectoral nerve blocks (Pecs I and Pecs II) are superficial thoracic wall blocks which block the pectoral and intercostal nerves. They can be used as analgesia/anesthesia for breast surgery and other procedures/surgeries involving the anterior chest wall (arteriovenous graft creation surgery, minimally invasive cardiac surgery and thoracotomy, etc.). The aim of this study is to evaluate publications in the scientific field of pectoral nerve blocks. ISI Web of Knowledge-Science was used for the analysis. All scientific works published included in the Science Citation Index Expanded (SCI-E) from 1975 to January 27, 2019, were analyzed. A retrospective search was performed using key words "pectoral nerve block," "PECS I," "PECS II," "pecs block," "PECS block,""Pecs I," "Pecs II," "PECS 1," "PECS 2," and "modified pecs I block." We further analyzed these results by the "analyze" function of the software in terms of number of papers for each country, type of documentation, number of publications per year, and name of journals and authors. The number of citations to published works was also calculated by using the citation function of the same software. 72 papers were found related to pectoral nerve block. The biggest contribution was from India (24.28%), and followed by Japan (14.28%), USA (14.28%), Canada (7.14%), Egypt (7.14%), Italy (5.71%), and South Korea (5.71%). The total number of publications increased sharply in years from 2014 (n = 1) to 2018 (n = 28). We have detected that papers on the use of pecs block in breast cancer surgery, which is one of the most common surgical procedure in the world, are few in the literature. With this study, we hope to increase the awareness on this area. We believe that pecs block applications will become widespread with the increasing use of ultrasound in anesthesia and the increase in education in this field.

Aggressive Mucinous Carcinoma of Male Breast Abstract We report of a mucinous carcinoma of the breast in a 62-year-old male, who presented with left breast mass and incisional biopsy scar. Incisional biopsy showed invasive mucinous carcinoma with endocrine differentiation. Patient underwent a simple mastectomy and sentinel lymph node biopsy (SLNB). In definitive pathologic examination, tumor showed estrogen- and progesterone-positive and her2-neu-negative receptor status. This was followed by adjuvant chemotherapy. After 2 weeks of the first cure chemotherapy treatment, patient admitted with respiratory distress and diagnosed as having thoracentesis requiring massive pleural effusion. In the detailed examination, multiple hepatic metastases were detected. In this report, we present a male patient with mucinous breast carcinoma and multiple distant metastases.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cannabis Research

Total and differential white blood cell count in cannabis users: results from the cross-sectional National Health and Nutrition Examination Survey, 2005–2016 Abstract Background Elevated white blood cell (WBC) count in tobacco cigarette smokers compared to non-smokers has been well documented, but little is known on circulating WBC counts and cannabis use. Methods The National Health and Nutrition Examination Survey (2005–2016) is designed to be nationally representative of United States non-institutionalized population. The current study includes adult participants 20–59 years of age (n = 16,430) who underwent a detailed examination in the mobile examination center (MEC). Cannabis use was measured using Audio Computer-Assisted Self-Interview. Cannabis use was classified into never, former, occasional (1–7 days of the past 30 days), and heavy (> 7 days of the past 30 days). WBC count was measured using the Coulter Counter method. Results Total WBC count was higher among heavy cannabis users when compared to never users (β = 189; 95% confidence interval: 74, 304, p = 0.001). Among circulating WBC types, modest differences were observed for neutrophil count. Neither former nor occasional cannabis use was associated with total or differential WBC counts. Conclusions A modest association between heavy cannabis use and WBC count was detected. Additional research is needed to understand the immune related effects of different modes of cannabis use and to elucidate the role of proinflammatory chemicals generated from smoking cannabis.

Journal of Cannabis Research : a new international, multi-disciplinary, open access journal

Cannabis use patterns at the dawn of US cannabis reform Abstract In the United States (US), three in 10 cannabis users develop cannabis use disorder (CUD). Usage patterns in line with CUD may be associated with socio-economic disadvantage, and other negative effects. Thus, research on CUD is paramount. To provide understanding around CUD, it is necessary to detail granular cannabis usage preferences, as some risk from cannabis use may be mitigated through informed behavioral choices by users. We describe cannabis usage preferences among US Global Drug Survey (GDS) respondents, primarily young men. The cross-sectional web-based GDS (2017) was completed by 8345 US-resident respondents (median age = 23, Interquartile Range 19–32; % male = 75.48) who reported cannabis use. Of those who reported cannabis use in the past year, most (78%) reported consuming their first joint more than an hour after waking, and about half the sample (49%) had their last joint 1–2 h before bed. Cannabis was used for a median of 250 days in the last year (almost daily). Respondents spent a median of four hours a day stoned when cannabis was used. High potency herbal cannabis was the preferred variant by 62% of participants. We suggest that frequent use of cannabis may increase risk of health harms, and highlight the need to mitigate problematic use. With the rapidly developing US cannabis market, possibly problematic usage patterns may indicate potential for CUD especially within young men.

High school student cannabis use and perceptions towards cannabis in southcentral Colorado – comparing communities that permit recreational dispensaries and communities that do not Abstract Currently, with the legalization of cannabis and the opening of recreational dispensaries in states across the country, the question of whether or not proximity to recreational cannabis dispensaries affects high school students in terms of their cannabis use, their perceptions of the accessibility of cannabis and their perceptions on the harmfulness and wrongfulness of using cannabis is particularly relevant and timely. In 2014 in Colorado, Amendment 64 went into effect and communities were allowed to legally permit recreational cannabis dispensaries; some communities agreed to permit the opening of recreational dispensaries while other communities did not. Using data from the cross-sectional Healthy Kids Colorado Survey collected from students in randomly selected high schools in both 2013 and 2015, data on student use and perceptions towards cannabis use was analyzed comparing communities that permitted recreational cannabis dispensaries and communities that did not. The random cross-sectional design used a 2X2 factorial ANOVA for each of the dependent factors: use, access, wrongfulness, and harm. There were a total of three communities that permitted recreational dispensaries, and within those three communities, data was collected from seven high schools. There were four communities that did permit recreational dispensaries, and within those four communities, data was collected from five high schools. The data were aggregated into two groups: 'yes' allows dispensaries, and 'no' does not allow dispensaries. These two groups were used as comparisons in the factorial ANOVA along with the two collection event years of 2013 and 2015. The analysis indicates differences between students in communities that have never permitted recreational cannabis dispensaries and students in communities that opened recreational dispensaries in 2014. Students in communities that permitted recreational dispensaries used more cannabis, thought cannabis was less harmful, less wrong, and was more difficult to access than high school students in communities that did not permit recreational cannabis dispensaries, however these differences existed before and after recreational dispensaries were introduced in 2014. Looking at each type of community to see if there was a change between 2013 and 2015, there were no statistically significant differences between students in 2013 and 2015 in each type of community with one exception; students in communities that did not permit recreational cannabis dispensaries felt even more strongly in 2015 that cannabis use is wrong compared to 2013. Based on the 2013 and 2015 Healthy Kids Colorado Survey data, permitting or not permitting recreational cannabis dispensaries in a community does not appear to change student cannabis use or perceptions towards cannabis.

Genetic tools weed out misconceptions of strain reliability in Cannabis sativa: implications for a budding industry Abstract Background Unlike other plants, Cannabis sativa is excluded from regulation by the United States Department of Agriculture (USDA). Distinctive Cannabis varieties are ostracized from registration and therefore nearly impossible to verify. As Cannabis has become legal for medical and recreational consumption in many states, consumers have been exposed to a wave of novel Cannabis products with many distinctive names. Despite more than 2000 named strains being available to consumers, questions about the consistency of commercially available strains have not been investigated through scientific methodologies. As Cannabis legalization and consumption increases, the need to provide consumers with consistent products becomes more pressing. In this research, we examined commercially available, drug-type Cannabis strains using genetic methods to determine if the commonly referenced distinctions are supported and if samples with the same strain name are consistent when obtained from different facilities. Methods We developed ten de-novo microsatellite markers using the "Purple Kush" genome to investigate potential genetic variation within 30 strains obtained from dispensaries in three states. Samples were examined to determine if there is any genetic distinction separating the commonly referenced Sativa, Indica and Hybrid types and if there is consistent genetic identity found within strain accessions obtained from different facilities. Results Although there was strong statistical support dividing the samples into two genetic groups, the groups did not correspond to commonly reported Sativa/Hybrid/Indica types. The analyses revealed genetic inconsistencies within strains, with most strains containing at least one genetic outlier. However, after the removal of obvious outliers, many strains showed considerable genetic stability. Conclusions We failed to find clear genetic support for commonly referenced Sativa, Indica and Hybrid types as described in online databases. Significant genetic differences within samples of the same strain were observed indicating that consumers could be provided inconsistent products. These differences have the potential to lead to phenotypic differences and unexpected effects, which could be surprising for the recreational user, but have more serious implications for patients relying on strains that alleviate specific medical symptoms.

Molecular neuroscience at its "high": bibliometric analysis of the most cited papers on endocannabinoid system, cannabis and cannabinoids Abstract Background Cannabis, cannabinoids and endocannabinoids are heavily investigated topics with many articles published every year. We aimed to identify the 100 most cited manuscripts among the vast literature and analyze their contents. Methods Web of Science (WoS) Core Collection was searched to identify the 100 most cited relevant manuscripts, which were analyzed with reference to (1) authorship, (2) institution, (3) country, (4) document type, (5) journal, (6) publication year, (7) WoS category, and (8) citation count. Semantic content and citation data of the manuscripts were analyzed with VOSviewer. Results The most cited manuscripts were published between 1986 and 2016, with the majority being published in the 2000s (n = 51). The number of citations for the top 100 articles ranged from 469 to 3651, with a median citation count of 635.5. The most prolific authors were Vincenzo Di Marzo (n = 11) and Daniele Piomelli (n = 11). The major contributing countries were USA (n = 49), Italy (n = 22), UK (n = 19), and France (n = 11). The most prolific institutions were University of California (n = 14), National Research Council of Italy (n = 12) and National Institutes of Health USA (n = 12). The manuscripts consisted of original articles (n = 75), reviews (n = 24) and a note (n = 1). The most dominant journal was Nature (n = 15). The major WoS categories associated were Multidisciplinary sciences (n = 31), Neurosciences (n = 20), Pharmacology / Pharmacy (n = 16), and General / Internal Medicine (n = 11). Conclusions The top-ranked manuscripts among the 100 were concerning analgesia, weight loss, long-term potentiation, depolarization-induced suppression of inhibition, opiates and other topics. Cannabinoid type 1 (CB1) receptor was studied by more of the top 100 papers in comparison to cannabinoid type 2 (CB2) receptor. The most frequently mentioned chemicals in these publications were 2-arachidonoylglycerol, tetrahydrocannabinol, and anandamide. Together, these manuscripts comprise the most highly cited publications in the topic, literally the molecular neuroscience at its "high".

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Psycho-Linguistic Research

The Voice and Speech Quality Correlates of Psychological Observations in Jungian Active Imagination Experiment Abstract Jungian active imagination is a well known and valuable method in analytical psychology and psychotherapy. The present study assessed, for the first time, psychological and psycho-acoustical (voice and speech quality) effects of active imagination experiment in outdoor, forest, ambient. In order to analyse the voice and speech quality, participants' verbal expressions were recorded before and after the experiment. Psychological observations were based on the thirteen features and were rated according to the bipolar Comparison Mean Opinion Score scale. The results showed a noticeable positive participants' experiences after the experiment, connected with themselves, others, their behaviour, other verbal and non-verbal expressions and relations towards nature. Voice and speech quality analysis, based on the speech signal processing approach, was done based on the fourteen acoustic features. The results showed a statistically significantly better voice and speech quality of the participants at the end of the experiment (p < 0.05). Applying the averaging model from the Information Integration Theory, we obtained integral evaluative ratings in active imagination for psychological observations EAI and voice and speech quality observations EVQ, for each participant. The value of Pearson's correlation coefficient R = 0.6385 (p < 0.05) has shown a significant correlation between these two ratings. Overall results highlight starting hypothesis that exist some strong voice and speech correlates of psychological observations in Jungian active imagination experiment.

Academic Vocabulary Knowledge and Reading Comprehension Skills Among Seventh-Graders in Arabic as L1 Abstract The current study attempted to investigate the contribution of an intervention program to fostering Arabic academic vocabulary knowledge and reading comprehension skills among seventh grade Arabic native speaking pupils. For this purpose, 247 pupils from four schools in northern Israel have participated in the study. Arabic literacy units that targeted academic vocabulary and reading comprehension skills were administrated for a period of 5 months. To assess the efficacy of the intervention program, academic vocabulary tests (receptive and productive) as well as reading comprehension test were administrated. As indicated by the results, the interventional group showed significantly higher performance in reading comprehension and productive academic vocabulary when compared to the control group. In contrast, no significant improvement was noted in receptive academic vocabulary knowledge. Taken together, the study results point to the contribution of comprehensive and direct academic vocabulary instructional approaches to promoting academic vocabulary knowledge and reading comprehension of academic texts. Moreover, it stresses the need for policy change and curricular adjustments in Arabic language instruction, acknowledging the importance of fostering academic language skills in the road to academic success.

On the Implicit Anaphoric Argument of Relational Nouns in Mandarin Chinese Abstract This paper provides experimental and theoretical evidence for the syntactic realization of an implicit possessor argument in Relational Nouns (RNs, e.g. father) in Mandarin Chinese. The results of Experiment 1 show that the antecedent of the implicit argument in RNs must be a noun phrase (NP) in the sentence where the RN is located, rather than an NP in the discourse context. Experiment 2 shows that the implicit argument of RNs must be bound by a c-commanding NP. The results exclude the possibility that the RNs' implicit argument is a pronominal that would link to a contextually salient NP and would not require a c-commanding referential antecedent. Rather, the experimental results show that the identification of the antecedent of the RNs' implicit argument is constrained by the same principle of binding theory that constrains the reflexive zìjǐ 'self', specifically requiring a c-commanding antecedent.

The Effects of Vocabulary Enhancement Exercises and Group Dynamic Assessment on Word Learning Through Lexical Inferencing Abstract The study aimed to explore the effect of group dynamic assessment on word learning through lexical inferencing and to compare it to that of vocabulary enhancement exercises. Through purposive sampling, 45 intermediate EFL learners were selected as participants and randomly assigned to three groups. The participants read six texts over a 6-day period and answered comprehension questions for each text. In the second phase of each treatment session, the first group engaged in lexical inferencing of the underlined words within group dynamic assessment framework. The second group did two vocabulary exercises for each target word. The third group engaged in lexical inferencing of target words through group dynamic assessment framework and also did one vocabulary exercise for each target word. Vocabulary Knowledge Scale (Wesche and Paribakht in Can Mod Lang Rev 53:13–40, 1996) was used to measure learners' knowledge of the target words 1 day prior to the treatment and 1 day and 28 days after the treatment. The results showed that in terms of gains in depth and size of vocabulary knowledge the first and the second groups were not significantly different. However, the third group significantly outperformed the first and the second groups. It was concluded that group dynamic assessment is as effective as vocabulary exercises in enhancing word learning through lexical inferencing and that the combination of group dynamic assessment and vocabulary exercises could enhance word learning through lexical inferencing even more.

Subject–Aux Inversion in Children with SLI Abstract An elicited production study investigated subject–aux inversion in 5-year-old children with specific language impairment (SLI) and 2 control groups, typically-developing 5-year-old children and 3-year-old children matched by mean length of utterance. The experimental findings showed that children with specific language impairment produced subject–aux inversion in yes/no questions significantly less often than either of the control groups. However, the fact that lack of inversion is reflected in the input led to the proposal that children with specific language impairment choose the most economical grammatical option. For main clause wh-questions, children with SLI carried out subject–aux inversion at a rate that was not significantly different from the control groups. This finding suggests that these children have access to hierarchical phrase structure representations for questions and the relevant movement operations. In embedded wh-questions, where subject–aux inversion is not permitted, children with SLI implemented SAI more frequently than the control groups. Our interpretation of this finding is that once children with SLI acquire the subject–aux inversion rule, that they are slower to learn that embedded clauses present an exception to the rule.

The Role of Short Vowels in Reading Arabic: A Critical Literature Review Abstract The purpose of the present review is to examine the studies that tested the role of short vowels in reading Arabic. Most of the studies are reviewed in this paper and two contradicted data are presented: data that support positive contribution of short vowels in reading Arabic, and the other data that reject the assumption that short vowels contribute to the quality of reading, and suggest that these short vowels do not add any positive contribution and maybe the opposite; short vowels hinder reading in Arabic orthography. The results are criticized indicating some methodological problems and suggestions for further studies are presented.

A Note on the Voice Mismatch Asymmetry in Ellipsis Abstract Theories of ellipsis differ in the identity condition claimed to hold between an antecedent and an elided constituent. A syntactic identity condition leads to the prediction that syntactic mismatches between an antecedent and elided constituent should give rise to a penalty, and that penalty should be greater than in corresponding examples without ellipsis. Further, if syntactic mismatches are ungrammatical, violating the syntactic identity condition, then in effect they are speech errors and would be expected to be rated higher when a passive clause antecedes an active elided VP than vice versa because people misremember passives as actives more often the reverse. A written acceptability judgment study crossed the voice of the antecedent clause (active/passive), the voice of the ellipsis clause (active/passive) and ellipsis/non-ellipsis in the final clause. Results indicate a syntactic mismatch lowers acceptability in examples with elided VPs but not examples with overt VPs, as predicted by theories with a syntactic identity condition. Passive-active mismatches were rated better than active–passive ones, especially with ellipsis, as predicted by a speech error/repair approach to mismatches. This result eliminates any concern that the appearance of a voice asymmetry might only be due to some incompatibility between VP ellipsis and passive voice.

Grammar, Gender and Demonstratives in Lateralized Imagery for Sentences Abstract We investigated biases in the organization of imagery by asking participants to make stick-figure drawings of sentences containing a man, a woman and a transitive action (e.g. she kisses that guy). Previous findings show that prominent features of meaning and sentence structure are placed to the left in drawings, according to reading direction (e.g. Stroustrup and Wallentin in Lang Cogn 10(2):193–207, 2018. https://doi.org/10.1017/langcog.2017.19). Five hundred thirty participants listened to sentences in Danish and made eight drawings each. We replicated three findings: (1) that the first mentioned element is placed to the left more often, (2) that the agent in the sentence is placed to the left, and (3) that the grammatical subject is placed to the left of the object. We further tested hypotheses related to deixis and gender stereotypes. By adding demonstratives (e.g. Danish equivalents of this and that), that have been found to indicate attentional prominence, we tested the hypothesis that this is also translated into a left-ward bias in the produced drawings. We were unable to find support for this hypothesis. Analyses of gender biases tested the presence of a gender identification and a gender stereotype effect. According to the identification hypothesis, participants should attribute prominence to their own gender and draw it to the left, and according to the stereotype effect participants should be more prone to draw the male character to the left, regardless of own gender. We were not able to find significant support for either of the two gender effects. The combination of replications and null-findings suggest that the left-ward bias in the drawing experiment might be narrowly tied to left-to-right distribution in written language and less to overall prominence. No effect of handedness was observed.

Willingness to Communicate: A Predictor of Pushing Vocabulary Knowledge from Receptive to Productive Abstract The issue of moving vocabulary knowledge from receptive to productive mode is among the most important but less studied strands of second or foreign language learning. The present study served as an attempt to shed light on this issue by taking into account the trait of willingness to communicate as an indicator of learners' capability in promoting their lexical knowledge from receptive to productive status. It, in fact, sought to examine the role of willingness to communicate, as a type of individual difference, in the receptive/productive vocabulary knowledge of learners. The hypothesis underlying the study is that WTC can be regarded as a good predictor for not only the degree of learners' receptive and productive lexical knowledge size, but also as an indication of learners' success in transition of their word knowledge from receptive to productive mode. To accomplish this, 104 Iranian EFL learners were chosen to act as the study participants. They were given three different instruments (one to identify their willingness to communicate degree, one for measuring receptive vocabulary knowledge, and one for calculating their productive knowledge). Having gathered and analyzed the intended data, the study showed that high and low willingness to communicate learners had almost the same receptive lexical knowledge. Furthermore, it was revealed that learners with high level of willingness to communicate had more productive vocabulary knowledge than those with low level of willingness to communicate. Lastly, the study implied that willingness to communicate might be taken as a predictor of learners' transition of lexical knowledge from receptive to productive mode.

The Development of Anaphora Resolution in Spanish Abstract The present study focuses on the development of Spanish pronominal processing. We investigate whether the pronoun interpretation problem (i.e., reflexive pronouns comprehension is resolved at an earlier age than that of personal pronouns, also known as the Delay of the Principle B Effect), which has been documented in other languages, also occurs in Spanish. For this purpose, we conducted two experiments including pronoun resolution tasks. In Experiment 1, a task adapted from the experimental paradigm proposed by Love et al. (J Psycholinguist Res 38:285–304, 2009. https://doi.org/10.1007/s10936-009-9103-9) was used, which examines the off-line processing of the Spanish pronouns se and le. In Experiment 2, on-line processing of the same pronouns was evaluated with eye-tracking, using a paradigm developed by Thompson and Choy (J Psycholinguist Res 38:255–283, 2009. https://doi.org/10.1007/s10936-009-9105-7). Forty-three participants aged 4–16 years completed both experiments. Results indicated that there is no developmental asymmetry in the acquisition of successful resolution of the two types of anaphora in Spanish: from age 4, reflexive and clitic pronouns are processed with the same degree of accuracy.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Bone and Mineral Metabolism

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation Abstract In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague–Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.

A meta-analysis of bone morphogenetic protein-2 versus iliac crest bone graft for the posterolateral fusion of the lumbar spine Abstract The impact of autologous iliac crest bone graft versus BMP-2 to improve fusion rates for posterolateral fusion (PLF) of the lumbar spine remains unanswered. Single-institution-centered data dominate the literature, providing results that may be contradictory or inconclusive. The aim of this paper is to analyze data pooled from multiple well-controlled studies that examined both ICBG and BMP-2 for use in PLF. This meta-analysis also provides details of success in different subsets of patients with variable risk factors for delayed and non-unions. Six high-quality randomized clinical trials were selected. Efficacy, morbidity, quality of life, and safety were compared between the BMP-2 group and the ICBG group. A total of 908 patients were included in the study. At 24 months, 94% of patients achieved fusion in the BMP-2 group and 83% in the ICBG group. At 6 and 12 months, the fusion was also greater in the BMP-2 group (86% vs. 60% and 88% vs. 80%, respectively). Surgical time, intraoperative blood loss, and hospitalization days also showed significant differences in favor of the experimental group (p < 0.01). There were no differences between two groups in the Oswestry Disability Index, 36-Item Short Form Health Survey and Back Pain Score, whereas a greater number of additional surgical procedures were performed in the ICBG group (p = 0.001). In conclusion, the use of BMP-2 in PLF reduced the surgical morbidity and had more beneficial effects on the fusion rate. The quality of life based on clinical scores was the same in both groups.

Urolithiasis increases the risk of subsequent onset of osteoporosis Abstract Urolithiasis and osteoporosis are two different pathological entities, but are both important public health issues in older patients. Moreover, the two diseases may share some similar pathogenesis pathway. Currently, few studies focus on the relationship between urolithiasis and osteoporosis. Furthermore, whether the common mobilities influence the long-term osteoporosis rate in urolithiasis patients has never been studied. In the present study, we used the Taiwan National Health Insurance Database (LHID 2000) compiled by the NHI from 1996 to 2013 to determine whether urolithiasis influenced long-term osteoporosis; controls were matched for age, sex, and other comorbidities (including hypertension, diabetes mellitus, dyslipidemia, liver disease, and cardiovascular disease). We included a total of 91,254 patients, including 22,575 patients with urolithiasis and 68,679 control patients. There was a significant difference between the incidence of osteoporosis between the urolithiasis and control groups (adjusted hazard ratio 1.34, 95% CI 1.19–1.79, p < 0.001) during the follow up. The incidence rate of osteoporosis during the follow-up period was 8.87 per 1000 person-years in the urolithiasis group and 6.37 per 1000 person-years in the control group. Based on our results, it is evident that urolithiasis significantly increases the subsequent osteoporosis rate. Though the clinical mechanisms are not fully understood, patients who have a history of urolithiasis may need regular follow-up assessment of bone marrow density.

Maternal 25-hydroxycholecalciferol during lactation improves intestinal calcium absorption and bone properties in sow-suckling piglet pairs Abstract Lower maternal vitamin D status during lactation is a common health problem. The objectives of this study were to investigate the effects of maternal 25-hydroxycholecalciferol (25-OH-D3) supplementation during lactation on maternal and neonatal bone health in a sow model. 32 Large White × Landrace sows were assigned randomly to one of two diets supplemented with 2000 IU/kg vitamin D3 (ND) or 50 μg/kg 25-OH-D3 (25-D). The experiment began on day 107 of gestation and continued until weaning on day 21 of lactation. Maternal 25-OH-D3 supplementation significantly decreased milk n-6:n-3 PUFA ratio, which supported bone formation of piglets. Supplementation with 25-OH-D3 altered bone turnover rate of sows and piglets, as evidenced by higher bone-specific alkaline phosphatase (BALP) concentration in serum. 25-D sows had significantly higher bone density and mechanical properties of tibias and femurs than ND sows. Calcium (Ca) absorption rate was higher in 25-D sows than ND sows, which was caused partially by the increased mRNA expressions of renal 1α-hydroxylase (CYP27B1) and duodenal vitamin D receptor (VDR), transient receptor potential vanilloid 6 (TRPV6), and calcium-binding protein D9k (CaBP-D9k). Maternal 25-OH-D3 supplementation increased tibial and femoral Ca content by up-regulating Ca-related gene expression in kidney (CYP27B1), ileum (VDR and claudin-2), and colon (VDR and CaBP-D9k), thus, activating 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3]-dependent Ca transport in piglets. In conclusion, improved milk fatty acids and higher mRNA expressions of calcitropic genes triggered by maternal 25-OH-D3 supplementation would be the potential mechanism underlying the positive effects of 25-OH-D3 on maternal and neonatal bone health.

Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament Abstract Although ossification of the posterior longitudinal ligament (OPLL) commonly develops in the cervical spine, it also occurs, albeit less commonly, in the thoracic spine. However, data are scarce regarding the characteristics of patients with thoracic OPLL. In the current study, we performed a cross-sectional study on a total of 133 patients with OPLL to clarify the clinical characteristics of patients with thoracic OPLL compared with those of patients with cervical OPLL. The subjects were divided into four groups according to the main region of OPLL and treatment type: C-OPLL-C, cervical OPLL treated conservatively; C-OPLL-S, cervical OPLL treated via surgery; T-OPLL-C, thoracic OPLL treated conservatively; and T-OPLL-S, thoracic OPLL treated via surgery. Symptoms developed at an earlier age in the T-OPLL-S group than in the C-OPLL groups. Current body mass index (BMI), maximum lifetime BMI, and BMI at the age of 20 years were significantly higher in the T-OPLL-S group than in the C-OPLL groups. Yearly weight gain from the age of 20 years to the age at which maximum body weight was attained was significantly greater in the T-OPLL-S group than in the C-OPLL groups. The T-OPLL group showed a higher rate of co-existence of OPLL at other regions or ossification of the ligamentum flavum compared to the C-OPLL groups. Our findings demonstrate that severe obesity, early-onset of symptoms, and diffuse ossification of spinal ligaments are distinct features of patients with myelopathy caused by thoracic OPLL.

Correction to: Re‑fracture and correlated risk factors in patients with osteoporotic vertebral fractures In the Original publication of the article, the funding ID has been incorrectly published as (815602390) in the Acknowledgements.

Effect of CBX7 deficiency on the socket healing after tooth extractions Abstract CBX7 is shown to down-regulate the expression of osteopontin (OPN) that is associated with osteoblast function. Here, we studied the role of CBX7 in the wound healing of tooth extraction socket in which osteoblast activity is critical via comparison between CBX7-knockout (CBX7−/−) mice and their wild-type (WT) counterparts of 6 weeks old with maxillary first molar extracted. Mice were euthanized at 7, 14, and 21 days after extractions, and alveolar sockets were assessed by semi-quantitative histomorphometry for hard tissue healing, including new bone fill (Masson's trichrome staining), osteoblast activity (OPN/osterix, Osx), osteoclast activity (tartrate-resistant acid phosphatase, TRAP), and for soft tissue healing, including blood vessels (alpha smooth muscle actin, α-SMA). Also, the bone microarchitecture was evaluated by micro-CT. In radiological analysis, CBX7−/− mice increased bone mass significantly more than WT mice did. Consistently, both the amount of new bone fill and OPN/Osx-immunopositive cells in the extraction sockets were significantly increased in CBX7−/− mice at each time point with respect to their WT siblings, while osteoclast number exhibited a trend of more increase in CBX7−/− mice at all time points as well. In agreement with enhanced bone formation during socket healing, significantly elevated α-SMA-immunopositive area was noted in CBX7−/− mice in contrast to WT mice. Taken together, these data suggest that CBX7 deficiency has a positive effect on tooth extraction socket healing.

Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan Abstract Limited data are available on the safety and efficacy of anti-resorptive agents, particularly once-monthly bisphosphonates, for use in osteoporotic patients with chronic kidney disease (CKD). We conducted a post hoc analysis of data from a 12-month, randomized, double-blind, phase III study to evaluate the safety and efficacy of once-monthly risedronate (RIS-OM) 75 mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75 mg were stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 90, ≥ 60 to < 90, or ≥ 30 to < 60 mL/min/1.73 m2). Safety endpoints were incidence of adverse events (AEs) and percent change from baseline in eGFR, serum creatinine, calcium, and phosphorus. Efficacy endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs). In 420 patients included (age 67.7 ± 6.7 years, women 98.8%), the incidence of all AEs, gastrointestinal disorders, acute phase reaction, non-vertebral fractures, and renal and urinary disorders was not significantly different among subgroups. Interaction between subgroups and time was significant for eGFR (p = 0.010) and serum creatinine (p = 0.001) but considered to be regression to the mean and clinically insignificant. BMD significantly increased while BTMs significantly decreased from baseline with a similar degree of change among the subgroups. In conclusion, RIS-OM 75 mg showed consistent safety and efficacy in suppressing bone turnover and increasing BMD in Japanese primary osteoporosis patients with mild-to-moderate CKD. These results should, however, be interpreted with caution because the number of patients with moderate CKD was limited.

The effect of testosterone itself and in combination with letrozole on bone mineral density in male rats Abstract Testosterone is an essential hormone to maintain bone integrity; however, the effect of aromatase enzyme in androgen-induced bone maintenance remains somewhat unclear. The present study evaluated the effect of testosterone itself and combined with letrozole, an aromatase inhibitor, on bone mineral density of male rats. Total of 48 male rats were divided into 4 equal groups (n = 12/group); sham group, O: orchiectomy, O + T: orchiectomized rats treated with testosterone, O + T + L: orchiectomized rats treated with combination of testosterone and letrozole. Bone density (BMD), bone markers, and vitamin D metabolism parameters were checked in all groups before and after the study. There was no significant difference in baseline values of these parameters, but at the end of the study there was a significant decrease in delta BMD at both lumbar and femor in orchiectomized rats in comparison with the sham group (p < 0.001, p < 0.001, respectively). Both testosterone and its combination with letrozole increased lumbar and femoral BMD of orchiectomized rats, with a higher increase in lumbar BMD in O + T group. CTX were higher in O group rats. The present study showed a major role for testosterone on BMD maintenance in male rats. However, testosterone has a potent effect on lumbar BMD, by the aromatization to estradiol.

Cortical bone mineral density is increased by the cathepsin K inhibitor ONO-5334, which leads to a robust increase in bone strength: results from a 16-month study in ovariectomised cynomolgus monkeys Abstract This study evaluated the long-term effects of the cathepsin K inhibitor ONO-5334 on bone mass and strength in ovariectomised (OVX) cynomolgus monkeys. Animals were assigned to one of the following six groups: Sham (non-OVX), OVX control treated with vehicle, ONO-5334 1.2, 6 or 30 mg/kg/day, p.o., or alendronate (ALN) 0.05 mg/kg/2 weeks, i.v. for 16 months. Peripheral quantitative computed tomography (pQCT) analysis revealed that ONO-5334 increased not only trabecular bone mineral density (BMD) but also cortical BMD in the distal radius and the lumbar vertebra. ONO-5334 and ALN suppressed the deterioration of trabecular architecture by micro-CT analysis in the distal radius. Assessments of bone strength showed that ONO-5334 increased maximum load at the distal and midshaft radius. The linear regression lines between bone mass and strength in the lumbar vertebra were tended to be shifted towards increasing bone strength in the ONO-5334 6 and 30 mg/kg groups compared with the ALN groups. This indicated that bone strength was higher in the ONO-5334 groups than the ALN group, even though bone mineral content (BMC) and BMD were comparable. Subpopulation analysis revealed that, at similar integral BMC or BMD level, cortical bone mass for ONO-5334 was higher than for ALN; the opposite effects were observed for trabecular bone. In conclusion, ONO-5334 preferentially increased cortical bone, which may provide a greater contribution to bone strength. Since these results support a different mode of action for ONO-5334 compared with that of ALN, ONO-5334 may offer new therapeutic options to patients with osteoporosis.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Dermatologic Surgery

Outcomes for Basal Cell Carcinoma Treated With Vismodegib Extended Alternate Day Dosing No abstract available

Commentary on Transungual Excision of Glomus Tumors No abstract available

Trends in the Incidence of Bowen Disease Based on a Single-Center Study in the Netherlands BACKGROUND Incidence trends of nonmelanoma skin cancer show an increase. Few data have been published about the incidence of Bowen disease (BD). Three previous studies, conducted more than 15 years ago in North America, found large variation in incidence rates in Caucasians, and trends over longer periods have never been studied. OBJECTIVE To estimate the incidence of BD in a Caucasian population in Northern Europe (Maastricht, the Netherlands) between 2003 and 2013. METHODS Primary and histologically confirmed BD, diagnosed in Maastricht, the Netherlands, in the years 2003, 2008, and 2013, was retrieved from a pathology database. Age-standardized and sex-specific incidence rates per 100,000 inhabitants were calculated by using the age distribution of the European standard population of 2013. RESULTS A statistically significant increase in the annual age-standardized incidence rates per 100,000 people was found from 8.1 (95% confidence interval [CI] 3.7–12.5) in 2003 to 68.9 (95% CI 57.2–80.7) in 2013 (p < .001). For women, there was an increase from 7.7/100,000 (95% CI 2.0–13.4) in 2003 to 76.8/100,000 (95% CI 60.2–93.5) in 2013, respectively (p < .001). An increase from 8.8/100,000 (95% CI 1.8–15.9) in 2003 to 59.2/100,000 men (95% CI 42.8–75.6) in 2013 (p < .001) was found. CONCLUSION These findings suggest an increase in the annual age-standardized incidence rates in BD. Address correspondence and reprint requests to: Maud H.E. Jansen, Department of Dermatology, Maastricht UMC+ | azM, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands, or e-mail: maud.jansen@mumc.nl The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

Mohs Micrographic Surgery at the Skin and Cancer Foundation Australia, 20 Years Later (1997–2017) BACKGROUND The availability of Mohs micrographic surgery (MMS) in Australia has increased dramatically since its inception in the 1980s. OBJECTIVE This study aimed to describe the evolution of MMS practices at the Skin and Cancer Foundation Australia (SCFA) over the past 20 years (1997–2017). METHODS Retrospective analysis of Mohs surgery cases at SCFA in 2017, 2007, and 1997, comparing data on sex, age, tumor type and site, initial tumor and final defect size, number of surgical stages and sections, and closure management. The present study is limited by being a retrospective analysis from a single institution. RESULTS There was a 415% increase in the number of Mohs surgery cases from 1997 to 2017, and a significant increase in Mohs surgery-treated squamous cell carcinoma. The preoperative tumor and final defect size have decreased. More side-to-side closures and fewer grafts are being performed over time. LIMITATIONS Retrospective analysis from a single institution. CONCLUSION Over the last 20 years, MMS has remained appropriate in its application and is being increasingly used for treatment of squamous cell carcinoma suggesting improved access. Address correspondence and reprint requests to: Thomas J. Stewart, BBioMedSc, MBBS, MMed, FRACGP, The Skin & Cancer Foundation Australia, 121 Crown Street Darlinghurst, Sydney, Australia, 2010, or e-mail: thomas_stewart@live.com The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

Cadaveric Skin Grafts May Greatly Increase the Healing Rate of Recalcitrant Ulcers When Used Both Alone and in Combination With Split-Thickness Skin Grafts BACKGROUND Leg ulcers that do not heal despite appropriate treatment are defined as recalcitrant ulcers. Large surface area, depth, and long duration represent some of most important factors impeding ulcer healing. After sharp debridement, dermal substitutes including skin from cadaver donors may increase the healing rate of recalcitrant ulcers reducing the risk of scar formation and recurrence. OBJECTIVE Assessing if, after sharp debridement, dermal substitutes including skin from cadaver donors may increase the healing rate of recalcitrant ulcers reducing the risk of scar formation and recurrence. PATIENTS AND METHODS Among patients admitted to our hospital for all types of chronic leg ulcers, we retrospectively reviewed the records of patients affected by recalcitrant ulcers (surface greater than 100 cm2, tissue loss involving epidermis, dermis, and subcutaneous tissue, duration longer than 1 year, and showing no healing tendency). After sharp debridement, the ulcers were covered by allografts with strict follow-up after discharge. Multiple allografts were performed when necessary, and a final autograft was applied in case of incomplete healing. RESULTS The records of 414 patients were analyzed. Forty-three patients were lost at follow-up, and the remaining 371 healed after 765 grafting procedures. In 163 patients, the ulcers healed by means of a final autograft. In all the remaining cases, allograft led to ulcer healing. CONCLUSION Allografts represent an effective treatment option in case of recalcitrant, large, deep and long-lasting leg ulcers. Address correspondence and reprint requests to: Giovanni Mosti, MD, Clinica MD Barbantini, Via del Calcio n.2, 55100 Lucca, Italy, or e-mail: giovanni.mosti10@gmail.com The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

Passive Stereophotogrammetry and Structured Light Scanning for 3-Dimensional Imaging in Dermatologic Surgery No abstract available

A Comparison of Apoptotic Activity for Follicular Unit Extraction Hair Grafts Stored in Different Holding Solutions No abstract available

Introduction No abstract available

Validated Assessment Scales for the Female Asian Calf BACKGROUND Clinical photonumeric scales have been developed and validated to objectively measure the effectiveness of aesthetic treatments in specific anatomical areas; however, these are based on the typical features of Caucasian patients. No clinical scale for Asian calf appearance currently exists. OBJECTIVE To develop and validate a calf assessment scale for use in the female Asian patient population. METHODS AND MATERIALS During 2 validation sessions, 13 raters assessed calf images of female Asian subjects (N = 35) viewed from behind with feet flat on the floor (at rest) and on tiptoes (dynamic). Images were rated from 0 (very slim, linear profile) to 4 (very severe convex profile). RESULTS Inter-rater and intra-rater reliability were "substantial" (≥0.6, intraclass correlation coefficient [ICC] and weighted kappa) for the calf—at rest, calf—dynamic, and calf summary score. Reliability was "substantial" for calf—at rest and calf–dynamic (≥0.6, ICC and weighted kappa) and "almost perfect" (0.85) for the calf summary score. BMI and calf circumference were highly correlated with scale ratings, and calf circumference was a significant predictor. CONCLUSION This new photonumeric assessment scale has value for assessing the female Asian calf, providing a standardized measure of calf appearance in clinical practice and clinical research settings. Address correspondence and reprint requests to: Kyle Seo, MD, PhD, Department of Dermatology, Seoul National University College of Medicine, 101 Daehak-Ro Jongno-Gu, Seoul, Korea, or e-mail: doctorseo@hotmail.com Supported by Merz Pharmaceuticals GmbH, Frankfurt, Germany. The authors received an honorarium for participating in the consensus meeting. The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

A Challenging Defect of the Nasal Ala No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com