CYP1B1-derived epoxides modulate the TRPA1 channel in chronic pain

Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury. Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro, and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia (DRG) neurons. TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079, and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1. This latter effect mapped to residues Y933, G939, and S921 of TRPA1. Intra-plantar injection of 19,20-EpDPA induced acute mechanical, but not thermal hypersensitivity in mice, which was also blocked by A967079. Similarly, Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury. These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.

Maternal Outcomes and Clinical Characteristics of COVID-19 in Korean Pregnant Women during the Early Period of the Pandemic

The present study aimed to compare the clinical characteristics and outcomes between pregnant women and non-pregnant women of childbearing age (20–49 years old) diagnosed with coronavirus disease 2019 (COVID-19) during the initial stage of the COVID-19 pandemic in the Republic of Korea. This nationwide observational study included the information of COVID-19 patients collected by the Korea Disease Control and Prevention Agency from January 2020 to April 2021. Among 5,647 COVID-19 patients, 2,444 (43.3%) were women of childbearing age and 19 were pregnant. None of the pregnant women died. However, 4 deaths occurred among non-pregnant women aged 20–49 years. None of the 19 pregnant women with COVID-19 were admitted to the intensive care unit: they were admitted to the general ward, and none of them required supplemental oxygen. In conclusion, none of the pregnant women with COVID-19 experienced severe infection or death, unlike non-pregnant women of childbearing age.

Chronic postthoracotomy pain in transapical transcatheter aortic valve replacement

Objective: Chronic postthoracotomy pain (CPTP) is a persistent, occasionally debilitating pain lasting >2 months following thoracic surgery. This study investigates for the first time the prevalence and clinical impact of CPTP in patients who have undergone a transapical transcatheter aortic valve replacement (TA-TAVR). Design: This was a single-institution, prospective observational survey and a retrospective chart review. Setting: The study was conducted in the University Hospital. Participants: Patients. Materials and Methods: A survey of 131 participants with either a previous TA TAVR or transfemoral (TF) TAVR procedure was completed. A telephone interview was conducted at least 2 months following TAVR; participants were asked to describe their pain using the Short-Form McGill Pain Questionnaire. Measurements and Main Results: Odds ratio (OR) was calculated using the proportions of questionnaire responders reporting “sensory” descriptors in the TA-TAVR versus the TF-TAVR groups. Results were then compared to individual Kansas City Cardiomyopathy Questionnaire (KCCQ12) scores and 5-min walk test (5MWT) distances. A total of 119 participants were reviewed (63 TF, 56 TA). Among TA-TAVR questionnaire responders (n = 16), CPTP was found in 64.3% of participants for an average duration of 20.5-month postprocedure (OR = 10, [confidence interval (CI) 95% 1.91–52.5];P = 0.003). TA-TAVR patients identified with CPTP had significant reductions in 5MWT distances (−2.22 m vs. 0.92 m [P = 0.04]) as well as trend toward significance in negative change of KCCQ12 scores OR = 18.82 (CI 95% 0.85–414.99;P = 0.06) compared to those without CPTP. Conclusions: CPTP occurs in patients undergoing TA-TAVR and is possibly associated with a decline quality of life and overall function.

Prospective Study of Central versus Peripheral Obesity in Total Knee Arthroplasty

PURPOSE: Body mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA. MATERIALS AND METHODS: We prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI. RESULTS: Tourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores. CONCLUSIONS: Inferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.

Preventing Construct Subsidence Following Cervical Corpectomy: The Bump-stop Technique

Cervical corpectomy is a viable technique for the treatment of multilevel cervical spine pathology. Despite multiple advances in both surgical technique and implant technology, the rate of construct subsidence can range from 6% for single-level procedures to 71% for multilevel procedures. In this technical note, we describe a novel technique, the bump-stop technique, for cervical corpectomy. The technique positions the superior and inferior screw holes such that the vertebral bodies bisect them. This allows for fixation in the dense cortical bone of the endplate while providing a buttress to corpectomy cage subsidence. We then discuss a retrospective case review of 24 consecutive patients, who were treated using this approach, demonstrating a lower than previously reported cage subsidence rate.

Diagnosis and treatment of osteochondral lesions of the ankle: current concepts / Diagnóstico e tratamento das lesões osteocondrais do tornozelo: conceitos atuais

ABSTRACT We conducted a wide-ranging review of the literature regarding osteochondral lesions of the ankle, with the aim of presenting the current concepts, treatment options, trends and future perspectives relating to this topic.

RESUMO Os autores fazem uma revisão ampla da literatura a respeito das lesões osteocondrais do tornozelo, com o intuito de expor os conceitos atuais sobre o tema, as opções de tratamento, as tendências e as perspectivas.

Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest.

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO3). The purpose of this study was to determine the relationships between total NaHCO3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short‑term clinical outcomes. Results: Seventy‑five patients (86%) received NaHCO3. Total NaHCO3 dose averaged 136 ± 112 mEq (range: 0.0–535 mEq) per patient. Total NaHCO3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = −0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO3 was a function of the severity and duration of metabolic acidosis. NaHCO3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO3 dose administered was unrelated to short‑term clinical outcomes.

Herpes viruses and human papilloma virus in nasal polyposis and controls / Herpesvírus e vírus do papiloma humano na polipose nasal e controles

ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p = 0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%,p = 0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

RESUMO INTRODUÇÃO: A rinossinusite crônica com pólipos é uma doença multifatorial de etiopatogênese ainda não definida. Existem dados contraditórios na literatura sobre a implicação potencial de elementos virais na etiologia de pólipos nasossinusais. OBJETIVO: Comparar a prevalência de herpes vírus humanos (1-6) e papiloma vírus humano em pacientes adultos com rinossinusite crônica com pólipos nasais (CRwNP) e controles saudáveis. MÉTODO: A presença de DNA viral foi avaliada por PCR em tempo real, em amostras de pólipos nasais de 91 pacientes com CRwNP e na mucosa das conchas nasais de 38 controles saudáveis. RESULTADOS: A positividade do EBV foi maior nos pólipos nasais (24/91; 26,4%) do que nos controles (4/38; 10,5%), mas a diferença não foi significante (p = 0,06). O HHV-6 apresentou positividade menor nos pólipos nasais (13/91; 14,29%) do que os controles (10/38; 26,32%), (p = 0,13). No grupo CRwNP, uma amostra foi positiva para o vírus herpes simples (HSV-1) (1/91; 1,1%), e uma para citomegalovírus (CMV) (1/91; 1,1%); e nenhuma amostra foi positiva no grupo controle. Não houve amostra positiva para HSV-2, VZV, HR-HPV (16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) e LR-HPV (6,11). CONCLUSÃO: Diferenças de positividade do EBV e HHV-6 entre pacientes com CRwNP e controles saudáveis não são estatisticamente significantes, enfraquecendo a probabilidade de sua implicação na patogênese da CRwNP.

Heterotopic Ossification Causing Radiculopathy after Lumbar Total Disc Arthroplasty

To date, no reports have presented radiculopathy secondary to heterotopic ossification following lumbar total disc arthroplasty. The authors present a previously unpublished complication of lumbar total disk arthroplasty (TDA) secondary to heterotopic ossification (HO) in the spinal canal, and they propose a modification to the McAfee classification of HO. The patient had undergone an L5/S1 lumbar TDA two years prior due to discogenic back pain. His preoperative back pain was significantly relieved, but he developed new, atraumatic onset radiculopathy. Radiographs and a computed tomography myelogram revealed an implant malposition posteriorly with heterotopic bone formation in the canal, causing an impingement of the traversing nerve root. Revision surgery was performed with implant extraction, L5/S1 anterior lumbar interbody fusion, supplemental posterior decompression, and pedicle screw fixation. The patient tolerated the procedure well, with complete resolution of the radicular leg pain. At a two-year follow up, the patient had a solid fusion without subsidence or recurrence of heterotopic bone. This case represents a novel pattern of heterotopic ossification, and it describes a previously unreported cause for implant failure in lumbar disc replacement surgery-reinforcing the importance of proper intraoperative component positioning. We propose a modification to the existing McAfee classification of HO after TDA with the addition of Class V and VI HO.

The Prevalence of Extra-cranial Carotid Artery Disease in Chronic Heart Failure.

Background: The prevalence of carotid disease in patients with heart failure (HF) has not been described. This may be of importance for the implementation of novel interventions for heart failure that require surgery close to the carotid artery. Objective: The aim of this study was to determine the prevalence of extra-cranial carotid artery stenosis (ECAS) in patients with HF. Methods: The study population comprised consecutive, patients with chronic stable HF due to left ventricular systolic dysfunction (LVSD). Patients were invited to have an ultrasound duplex scan of the internal and common extra-cranial carotid arteries (ECA) and stenoses were classified as minor if <50%, moderate if 50-69% and severe if >70%. Results: Of 102 patients, the median age was 73 (IQR: 66-78) years and 95 were men. Ten patients had moderate ECAS of whom one also had severe ECAS in the contra-lateral artery. Thirteen patients gave a prior history of stroke or transient ischaemic attack. Of patients with ECAS, only three (30%) had had a neurological event and only three (23%) of those with a neurological event had moderate or severe ECAS (95% CI; 6-55%). Most neurological events had occurred in patients without ECAS. Conclusion: There is a moderately high prevalence of ECAS in patients with HF. However, most patients with chronic heart failure (CHF) who have had a neurological event do not have ECAS and most patients with ECAS do not have neurological symptoms. The value of screening for and management of ECAS in patients with HF remains to be established.

Surgical outcomes for perforated peptic ulcer: a prospective case series at an academic hospital in Monrovia, Liberia

Introduction The incidence of perforated peptic ulcer remains high in low and middle-income countries. Mortality can be significant; and early surgical management with careful evaluation of pre-operative risk factors is essential. The purpose of this study was to describe the clinical outcomes of surgical treatment for perforated peptic ulcer disease in Liberia and to explore risk factors for adverse outcomes.Methods This study prospectively examined 20 consecutive patients undergoing primary closure with omental patch for perforated pre-pyloric or duodenal peptic ulcer at the John F. Kennedy Medical Centre (JFKMC) in Monrovia; Liberia from May 2009 to March 2010. Pre-operative information was captured in a questionnaire. Risk factors were assessed for univariate and multivariate associations with in-hospital mortality.Results Median age was 33 years and 85 were males. A majority of the patients (70) had a history of gastritis and antacid use. Median time from beginning of symptoms to surgery was 4.5 days. Over-all in-hospital mortality following surgical therapy for perforated peptic ulcer disease was 35. Median length of stay among survivors was 16 days; and death occurred at median 1 day after admission. Long symptom duration and age 30 years of age were significantly associated with in-hospital mortality on univariate (? = 2.60 [0.18-5.03]; p = 0.035) and multivariate testing (? = 2.95 [0.02-5.88]; p =0.049). Conclusion Peptic ulcer disease and its treatment represent a potentially substantial source of morbidity and mortality in limited-resource settings. In this case series; surgical treatment for perforated peptic ulcer disease carried a high mortality; and the results highlight the potential for public health systems strengthening to prevent poor health outcomes. Peptic ulcer disease in low- and middle-income countries presents unique epidemiology and treatment challenges that may differ significantly from evidence-based guidelines in high-income countries

Yasuní - a hotspot for jaguars Panthera onca (Carnivora: Felidae)? Camera-traps and jaguar activity at Tiputini Biodiversity Station, Ecuador / Yasuní - Un hotspot para jaguares Panthera onca (Carnivora: Felidae)? Cámaras trampa y actividad del jaguar en la Estación de Biodiversidad Tiputini, Ecuador

Jaguars (Panthera onca) are the largest predator in lowland forests of Amazonia but there have been few studies on their occurrence and activity in such forests. Here, we used camera traps to document the occurrence and activity of jaguars within a local area (~650ha) of lowland forest of Eastern Ecuador, over two sample periods (2005-2008, 7 222 trap days; 2010-2012, 6 199 trap days). We accumulated 151 independent photos of jaguars (189 total photographs) that represented 21 different individuals, including 11 males (114 photographs), seven females (32 photographs), and three that could not be assigned to a sex. Individual jaguars varied in the number of months they were recorded in the area; ten were photographed in only one month; five were photographed over periods of 8 to 22 months; and five from 45 to 81 months. Capture rates across all camera stations averaged 10.6/1 000 trap days; capture rates did not differ between the two sample periods. Male jaguars were more active during the day (06:00am-18:00pm; 71% of photographs), whereas females were equally active during the day and night. Monthly activity was variable but showed no consistent pattern. Although the study area is much smaller than typical home ranges of jaguars, the area is clearly visited by a large number of different individuals, some of whom repeatedly visit the area, indicating that it forms part of their home range. Other individuals likely were simply passing through the area. Based on the number of jaguars recorded during this study, it is clear that the region is an important area for conservation. Continued protection will be needed to ensure that populations of jaguars and other species remain viable. Rev. Biol. Trop. 62 (2): 689-698. Epub 2014 June 01.

El jaguar (Panthera onca) es el depredador más grande de los bosques bajos de la Amazonía, pero existen pocos estudios sobre su presencia y actividad en los mismos. En este estudio utilizamos cámaras trampa para documentar la presencia y actividad de jaguares dentro de una área de bosque bajo de la Amazonía este de Ecuador (~650 ha) en dos períodos (2005-2008, 7 222 trampas noche; 2010-2012, 6 199 trampas noche). Acumulamos 151 fotos independientes de jaguares (189 fotografías en total) que representaron 21 individuos, incluyendo 11 machos (114 fotos), siete hembras (32 fotos) y tres a los que no se les pudo asignar sexo. Los jaguares individuales variaron en el número de meses en que fueron registrados en el área; diez fueron fotografiados solo en un mes; cinco fueron fotografiados en un periodo entre 8 y 22 meses; y cinco jaguares entre 45 y 81. Las tasas de captura a través de las estaciones de trampeo promediaron 10.6/1 000 trampas noche; las tasas de captura no presentaron diferencias en los dos períodos de muestreo. Los jaguares machos fueron más activos durante el día (06:00am-18:00pm; 71% de las fotografías) mientras que las hembras fueron igualmente activas tanto en el día como en la noche. La actividad mensual fue variable pero no mostró un patrón consistente. Aunque el área de estudio es mucho más pequeña que el rango de vida típico para un jaguar, el área es claramente visitada por un alto número de individuos diferentes, algunos de los cuales visitan repetidamente el lugar, indicando que este forma parte de su rango de vida. Es probable que otros individuos solamente sean transeúntes del área.

Fournier?s gangrene - delayed pedicle flap based upon the anterior abdominal wall

Introduction Fournier’s gangrene is a poly-microbial necrotizing fasciitis that involves the perineum and/or external genitalia. Urgent surgical debridement is well recognized as essential acute treatment yet unique challenges arise for plastic surgical reconstruction to obtain a complete functional recovery. This case describes a successful delayed pedicle flap repair based upon the anterior abdominal wall. Case description A 24 year old man was admitted to ICU ten days after elective circumcision with Fournier’s gangrene. He underwent a number of surgical debridements, and was referred for plastic surgical management. He had penile reconstruction using a random pattern abdominal flap, which was performed as a three stage procedure including flap vascular delay technique. Discussion Perineal and penile skin loss can be significant and is difficult to repair. Various techniques have been used to reconstruct lost tissue: skin grafts, transposition of the testes and spermatic cords to the thigh, flaps, and other types of pediculated myocutaneous flaps. Muscle flap reconstruction provides an environment that allows for complete regeneration of the urethral epithelium but is bulky and unsightly. Skin grafts contract and may produce painful and dysfunctional reconstructions. This novel technique produces a functional, and aesthetic reconstruction. Conclusion Penile skin recovery following Fournier’s gangrene recovery is problematic. This case demonstrates the functionality of a delayed flap repair using the anterior abdominal wall. .

Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies / 癌症

The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation allows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

Invasive Staphylococcus Aureus Infections in Diabetes Mellitus : Review

Staphylococcus aureus; the most virulent of the many staphylococcal species; has remained a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. S. aureus causes disease through both toxin-mediated and non-toxin-mediated mechanisms. This organism is responsible for both healthcare-associated and community-based infections ranging from relatively minor skin and soft tissue infections to severe life-threatening systemic infections. Patients with diabetes mellitus are at increased risk of invasive S aureus infections. This article focuses on the spectrum of invasive S aureus infections and discusses the clinical features; investigations and management of these infections in patients with diabetes mellitus

The Non-Surgical Treatment of Peyronie Disease: 2013 Update

Peyronie disease is a common cause of penile deformity and sexual dysfunction. Although surgery is regarded as the definitive management for this condition, there are many medical and minimally invasive therapies available, with widely varying efficacy reported in the literature. The purpose of this review is to describe the current state-of-the-art for each of the most commonly used as well as several developing non-surgical treatments. Further, we hope to offer perspectives that will aid practitioners in deciding among these treatments that are either already in use or have the potential to be used as alternatives to surgery in the management of this frustrating disease.

Optimized mixture of hops rho iso-alpha acids-rich extract and acacia proanthocyanidins-rich extract reduces insulin resistance in 3T3-L1 adipocytes and improves glucose and insulin control in db/db mice

Rho iso-alpha acids-rich extract (RIAA) from Humulus lupulus (hops) and proanthocyanidins-rich extracts (PAC) from Acacia nilotica exert anti-inflammatory and anti-diabetic activity in vitro and in vivo. We hypothesized that a combination of these two extracts would exert enhanced effects in vitro on inflammatory markers and insulin signaling, and on nonfasting glucose and insulin in db/db mice. Over 49 tested combinations, RIAA:PAC at 5:1 (6.25 microg/mL) exhibited the greatest reductions in TNFalpha-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to 5 microg/mL troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination (5 microg/mL) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to 5 microg/mL pioglitazone or 901 microg/mL aspirin. Finally, db/db mice fed with RIAA:PAC at 5:1 (100 mg/kg) for 7 days resulted in 22% decrease in nonfasting glucose and 19% decrease in insulin that was comparable to 0.5 mg/kg rosiglitazone and better than 100 mg/kg metformin. RIAA:PAC mixture may have the potential to be an alternative when conventional therapy is undesirable or ineffective, and future research exploring its long-term clinical application is warranted.

Total Knee Arthroplasty in Hemophiliacs: Gains in Range of Motion Realized beyond Twelve Months Postoperatively

BACKGROUND: Hemophiliacs have extrinsic tightness from quadriceps and flexion contractures. We sought to examine the effect of a focused physical therapy regimen geared to hemophilic total knee arthroplasty. METHODS: Twenty-four knees undergoing intensive hemophiliac-specific physical therapy after total knee arthroplasty, at an average age of 46 years, were followed to an average 50 months. RESULTS: For all patients, flexion contracture improved from -10.5 degrees preoperatively to -5.1 degrees at final follow-up (p = 0.02). Knees with preoperative flexion less than 90 degrees were compared to knees with preoperative flexion greater than 90 degrees. Patients with preoperative flexion less than 90 degrees experienced improved flexion (p = 0.02), along with improved arc range of motion (ROM) and decreased flexion contracture. For those patients with specific twelve-month and final follow-up data points, there was a significant gain in flexion between twelve months and final follow-up (p = 0.02). CONCLUSIONS: Hemophiliacs with the poorest flexion benefited most from focused quadriceps stretching to a more functional length, with gains not usually seen in the osteoarthritic population. This data may challenge traditional views that ROM gains are not expected beyond 12-18 months.

Unilateral cleft lip and nasal repair: techniques and principles

The Mashhad University of Medical Sciences and the Sheikh Hospital in Mashhad sponsored a Cleft Lip and Palate Workshop 30 April - 1 May 2009. During the Workshop, 6 surgical cases were performed and televised live to the audience attending the conference. Two of those cases were unilateral cleft lip repairs. The surgical technique used to repair these patients by the primary author [JGM] is a hybrid technique. It has evolved over the last decade as a result of prior surgical literature as well as first hand observation of various surgical colleagues. The following manuscript describes the surgical technique used at the Cleft Workshop in a step-wise or atlas-like fashion. The technique portion of the paper describes the repair of the unilateral cleft lip and nasal deformity in roughly the order the first author typically performs the procedure. More importantly, the final section of the paper details the principles that form the foundation for the techniques described

Family planning in sub-Saharan Africa: progress or stagnation?

Objective To review progress towards adoption of contraception among married or cohabiting women in western and eastern Africa between 1991 and 2004 by examining subjective need; approval; access and use. Methods Indicators of attitudes towards and use of contraception were derived from Demographic and Health Surveys; which are nationally representative and yield internationally comparable data. Trends were examined for 24 countries that had conducted at least two surveys between 1986 and 2007. Findings In western Africa; the subjective need for contraception remained unchanged; about 46of married or cohabiting women reported a desire to stop and/or postpone childbearing for at least two years. The percentage of women who approved of contraception rose from 32 to 39 and the percentage with access to contraceptive methods rose from 8 to 29. The proportion of women who were using a modern method when interviewed increased from 7 to 15(equivalent to an average annual increase of 0.6 percentage points). In eastern African countries; trends were much more favourable; with contraceptive use showing an average annual increase of 1.4 percentage points (from 16in 1986 to 33in 2007). Conclusion In western Africa; progress towards adoption of contraception has been dismally slow. Attitudinal resistance remains a barrier and access to contraceptives; though improving; is still shockingly limited. If this situation does not change radically in the short run; the United Nations population projections for this subregion are likely to be exceeded. In eastern Africa; the prospects for a future decline in fertility are much more positive