Emerging artificial intelligence-aided diagnosis and management methods for ischemic strokes and vascular occlusions: A comprehensive review.

Large-vessel occlusion (LVO) stroke is a promising field for the use of AI, especially machine learning (ML) because optimal results are highly dependent on timely diagnosis, communication, and treatment. In order to better understand the current state of artificial intelligence (AI) in relation to LVO strokes, its efficacy, and potential future applications, we searched relevant literature to perform a comprehensive evaluation of the topic. The databases PubMed, Embase, and Scopus were extensively searched for this review. Studies were then screened using title and abstract criteria and duplicate studies were excluded. By using pre-established inclusion and exclusion criteria, it was decided whether or not to include full-text papers in the final analysis. The studies were analyzed, and the relevant information was retrieved. In recognizing LVO on computed tomography, ML approaches were very accurate. There is a shortage of AI applications for thrombectomy patient selection, despite the fact that certain research accurately evaluates individual patient eligibility for endovascular therapy. Machine learning algorithms may reasonably predict clinical and angiographic outcomes as well as associated factors. AI has shown promise in the diagnosis and treatment of people who have just suffered a stroke. However, the usefulness of AI in management and forecasting remains restricted, necessitating more studies into machine learning applications that can guide decision making in the future.

Perception of Health-Care Professionals on Presumed Consent in Formulation of Proper Organ Transplantation Regulatory System.

Background: Owing to the advancement in organ transplantation, treating an individual with organ failure in today's world has become possible. However, organ transplantation is lagging in the absence of adequate organ donations. Shortage of organs for transplantation is a challenge to developing countries like Nepal and developed countries like the USA and UK. Despite various efforts to increase the rate of organ donation, the problem persists. The primary reason for the failure to accomplish adequacy in organ do-nation is the immediate dependency on an available donor. On top of that, reluctance to decide on organ donation after death, regarded as an onerous moment, at least by the general public, has another impact on the subject. Some countries have shifted while some are planning to change from an informed consent system to a presumed consent system, in which if an individual does not make any decision during life-time, it is presumed that his/her organ can be removed for organ transplantation after death. Objective: To perceive the perception of healthcare professionals of the tertiary care centre of eastern Nepal regarding the presumed consent system. Methods: Purposive sampling of 221 health care professionals (Faculties, Nursing In-charges, Lab-technicians, and Radiology technicians) participated in the study. Results: Most healthcare professionals (90.5%) support using a presumed consent system in Nepal and agree on considering the family's opinion in the decision-making for cadaveric organ donation. Conclusion: Most healthcare professionals have shown their perception in favors of presumed consent to support the increasing organ donation rate.

Analysis of Prognostic Factors of Bell's Palsy in a Tertiary Care Centre of Eastern Nepal.

Background Bell's palsy is the most common cause of acute facial peripheral neuropathy commonly encountered in otolaryngology clinics. Studies regarding epidemiology, risk factors, treatment and prognosis of Bell's palsy are sparse in our settings. Objective To analyze the prognostic factors of Bell's palsy in tertiary care Centre of eastern Nepal. Method A retrospective chart review of patients diagnosed with Bell's palsy from 1st January 2005 to 31st December 2018 was done. Records of the patients were obtained from medical record section of BP Koirala Institute of Health Sciences. Result A Total of 208 patients were included for analysis. After six months 72.6% patients had complete recovery. Patients who presented with lower House Brackmann (HB) grade had significantly better complete recovery than those with high grade (89.1% vs 45.6%). The complete recovery was 80.3%, 73.8%, 63.5% and 50% for the patients of more than 30 yrs, 31-45 years, 46-60 years and more than 60 years respectively and the difference was significant (p= 0.012). Alcohol significantly reduced the complete recovery (p= 0.043). Multivariate analysis showed high HB grade score at presentation to be significant predictor of poor prognosis. (p= 0.001 odds ratio 11.262). Conclusion Old age, use of alcohol and the severity of facial nerve palsy at the time of presentation were the bad prognostic factors, severity of the palsy was found to be most significant predictor.

Anastomosis for distal gastrectomy in Chinese patients: uncut roux-Y or roux-Y?

BACKGROUND: An appropriate method of anastomosis is crucial for gastric cancer patients who require gastrojejunal anastomosis. Surgeons have proposed different types of modified gastrojejunostomies in the last two decades. We focused on two types of standard anastomosis, i.e., Uncut Roux-Y and Roux-Y gastrojejunostomies, and compared the differences in immediate postoperative complications between the two types. METHODS: This is a retrospective study on 236 gastric cancer patients who underwent curative distal gastrectomy with gastrojejunal Roux-Y or Uncut Roux-Y anastomosis for six consecutive years. Immediate postoperative complications were compared between the two groups. The authors discussed the causes of the significant complications and their management. RESULTS: There was no difference in demographics between the two groups (92 Roux-y Versus 144 Uncut Roux-y). The overall complication rate was 20.8% with 1.4% anastomotic leakage in the Uncut Roux-Y group versus 33.7% with 7.6% anastomotic failures in the Roux-Y group (p < 0.05). More abdominal infections occurred in the Roux-Y anastomosis group compared with the Uncut Roux-Y anastomosis group (p < 0.05). Duration of postoperative stay was significantly longer in patients with Roux-y anastomosis group (p < 0.05). CONCLUSIONS: Considering the surgical simplicity and postoperative complications, the Uncut Roux-Y is a better choice for anastomosis in patients with gastric cancer undergoing gastrojejunostomy. A well-designed large cohort in a multi-centre randomized controlled trial is necessary to support these findings and compare other aspects.

Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. METHODS: A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. KEY POINTS: • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

Antioxidative and antibacterial peptides derived from bovine milk proteins.

The search for alternative preservatives is on the rise due to safety issues linked with the application of synthetic antioxidants and the extensive increase in bacterial resistance to several conventional antibiotics. Therefore, the quest for finding suitable alternatives including bioactive peptides has received attention. This article reports a comprehensive insight concerning antioxidative and antibacterial peptides derived from milk proteins, a prolific source of peptides having various bioactivities. Caseins and whey proteins have also been evaluated for antioxidative and antibacterial potential using the BIOPEP database. A notable number of potentially active peptides are present in milk proteins. Technological approaches are here reported for the production of these peptides. The findings of this review show potentiality of utilizing dairy derived antioxidative and antibacterial peptides in the development of a superior alternative to the current generation of preservatives and therapeutic agents, as well as a functional ingredient in dietetic or pharmaceutical applications.

Development of a Valid and Reliable Questionnaire to Identify Professional Opinion Regarding Organ Transplantation System.

BACKGROUND: Currently, the Nepalese law permits organ donation by an individual who falls into the category of a "close relative" of the recipient. There is a need for expansion of the live organ donor pool beside close relatives. Different systems of organ transplantation are followed by several countries and the professional opinions that underpin these systems need to be studied. OBJECTIVE: To generate a questionnaire related to different organ transplant systems and validate it so that it can be used to collect mass professional opinions. METHODS: Item generation, item reduction, item scaling, and pretesting were used to develop a questionnaire. The final version of the questionnaire was reviewed by experts for its content validity and then was used twice for participants at a 20-day interval to calculate Cronbach's alpha for testing its internal consistency and Intra-class correlation for testing its test and retest reliability. RESULTS: The questionnaire was found to be valid and reliable with an overall Cronbach's alpha of 0.701. Intra-class correlation scores for each question in both test and retest were correlated. CONCLUSION: A valid and reliable questionnaire was developed that can be used to collect mass professional opinions to assist policy makers to establish a better organ transplant system.

Non-Surgical Pneumoperitoneum.

Pneumoperitoneum is mostly caused by visceral perforation and surgical intervention; however non-surgical pneumoperitoneum has been reported without evidence of visceral disease. Blunt chest trauma causing an abrupt rise in thoracic pressure can leak air through the microscopic diaphragmatic defects or the mediastinum along perivascular connective tissue and cause pneumoperitoneum. We hereby present a case of non-surgical pneumoperitoneum after blunt chest trauma that was brought to the emergency department of college of medical sciences teaching hospital with features of bilateral pneumothorax with subcutaneous emphysema and abdominal distension which was diagnosed and managed promptly with bilateral chest drain and other supportive treatments.

Effect of pineapple waste powder on probiotic growth, antioxidant and antimutagenic activities of yogurt.

Although many fruit by-products are good sources of nutrients, little is known about their prebiotic potential. This research was aimed at establishing the prebiotic effect of pineapple wastes on probiotics including Lactobacillus (L.) acidophilus (ATCC® 4356™), L. casei (ATCC® 393™) and L. paracasei spp. paracasei (ATCC® BAA52™) and the subsequent release of antioxidant and antimutagenic peptides in yogurt during their growth. Oven- and freeze- dried peel and pomace were milled separately into powders and tested for prebiotic activities. The net probiotic growth (1.28-2.14 log cfu/g) in customized MRS broth containing the pineapple powders as a direct carbohydrate source was comparable to MRS broth containing glucose. The powders were also separately added to milk during the manufacturing of yogurt with or without probiotics. An increase (by 0.3-1.4 log cycle) in probiotic populations was observed in the yogurts as a consequence of pineapple powder supplementation. Crude water-soluble peptide extracts, prepared by high-speed centrifugation of the yogurts, displayed remarkable antioxidant activities assessed through in vitro assays, namely scavenging activity of 1,1-diphenyl-2-picrylhydrazyl radicals (IC50 = 0.37-0.19 mg/ml) and hydroxyl radicals (58.52-73.55 %). The peptide extracts also exhibited antimutagenic activities (18.60-32.72 %) as sodium azide inhibitor in the Salmonella mutagenicity test. Together, these results suggest that pineapple by-products exhibited prebiotic properties and could possibly be commercially applied in new functional food formulations.

Antibacterial and antiproliferative peptides in synbiotic yogurt-Release and stability during refrigerated storage.

The search for alternative therapeutics is on the rise due to the extensive increase in bacterial resistance to various conventional antibiotics and side effects of conventional cancer therapies. Bioactive peptides released from natural sources such as dairy foods by lactic acid bacteria have received attention as a potential source of biotherapeutic peptides. However, liberation of peptides in yogurt depends on proteolytic activities of the cultures used. Thus, this research was conducted to establish generation of inhibitory peptides in yogurt against pathogenic bacteria and cancer cells during storage at 4°C for 28d. Water-soluble crude peptide extracts were prepared by high-speed centrifugation of plain and probiotic yogurts supplemented with or without pineapple peel powder (PPP). The inhibition zones against Escherichia coli and Staphylococcus aureus by PPP-fortified probiotic yogurt at 28d of storage were, respectively, 25.89 and 11.72mm in diameter, significantly higher than that of nonsupplemented control yogurts. Antiproliferative activity against HT29 colon cancer cells was also significantly higher in probiotic yogurt with PPP than in nonsupplemented probiotic yogurt. Overall, crude water-soluble peptide extracts of the probiotic yogurt with PPP possessed stronger inhibitory activities against bacteria and cancer cells than controls, and these activities were maintained during storage. However, activities were lowered substantially during in vitro gastrointestinal digestion. These findings support the possibility of utilizing dairy-derived bioactive peptides in the development of a superior alternative to the current generation of antibacterial and anticancer agents, as well as a functional ingredient in foods, nutraceuticals, and pharmaceuticals.

Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

BACKGROUND: Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. METHODS: This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. RESULTS: 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees,14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. CONCLUSION: Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults.

Effect of refrigerated storage on probiotic viability and the production and stability of antimutagenic and antioxidant peptides in yogurt supplemented with pineapple peel.

Fruit by-products are good resources of carbohydrates, proteins, vitamins, and minerals, which may function as growth nutrients for probiotic bacteria. This research aimed at evaluating effects of pineapple peel powder addition on the viability and activity of Lactobacillus acidophilus (ATCC 4356), Lactobacillus casei (ATCC393), and Lactobacillus paracasei ssp. paracasei (ATCC BAA52) in yogurts throughout storage at 4°C for 28d. Plain and probiotic yogurts supplemented with or without pineapple peel powder or inulin were prepared. The probiotic counts in supplemented yogurts at 28d of storage ranged from 7.68 and 8.03 log cfu/g, one log cycle higher compared with nonsupplemented control yogurt. Degree of proteolysis in synbiotic yogurts was significantly higher than plain yogurts and increased substantially during storage. Crude water-soluble peptide extract of the probiotic yogurt with peel possessed stronger antimutagenic and antioxidant activities [evaluated measuring reducing power and scavenging capacity of 1,1-diphenyl-2-picrylhydrazyl; 2,2'-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid), and hydroxyl radicals] than control and maintained during storage. Pineapple peel, a by-product of juice production, could be proposed as a prebiotic ingredient in the manufacture of yogurts with enhanced nutrition, and functionality.

Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with (18)F-fludeoxyglucose (FDG-PET/CT) in a population with suspected graft infection and to validate a new diagnostic imaging score for FDG-PET/CT. METHODS: This was a prospective cohort study. FDG-PET/CT was performed prospectively in 34 patients with suspected graft infection, in 12 of them before the start of antimicrobial treatment. Diagnostic accuracy was assessed using a new five point visual grading score and by using a binary score. Maximum standardized uptake values (SUVmax) were calculated for quantitative measurements of metabolic activity, and cut off points were calculated using the receiver operator curve (ROC). The standard of reference was a microbiological culture, obtained after open biopsy or graft explantation. RESULTS: Using the new scale, FDG-PET/CT correctly recognized 27 patients with graft infection, one patient was diagnosed as false positive, six patients were correctly classified as true negative, and no patients were rated false negative. Hence, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of FDG-PET/CT for the diagnosis of graft infections were 100%, 86%, 96%, 100%, and 97%, respectively. Using a previously established binary score, sensitivity, specificity, PPV, NPV, and accuracy were 96%, 86%, 96%, 86%, and 94% respectively. ROC analysis suggested an SUVmax cut off value of ≥3.8 to differentiate between infected and non-infected grafts (p < .001). Additionally, FDG-PET/CT provided a conclusive clinical diagnosis in six of seven patients without graft infection (i.e., other sites of infections). CONCLUSIONS: The diagnostic accuracy of FDG-PET/CT in the detection of aortic graft infection is high. A newly introduced five point visual grading score and early imaging prior to antimicrobial treatment may further improve the diagnostic accuracy.

Treatment of Chronic Venous Ulcers Using New Four Layers Compressive Bandage Dressing.

INTRODUCTION: Lower-extremity ulcers represent the largest group of ulcers presenting to an outpatient department. It is a cumbersome, difficult to treat disease, which causes high morbidity and huge cost for the patient and healthcare system. Current standard treatment includes compression therapy.  However, majority of patients need long term treatment with minimal efficacy. Aim of our study is to evaluate efficacy of four layers compressive bandages for the management of chronic venous ulcers. METHODS: In Group A, we have prospectively included 20 patients with chronic venous ulcers on lower limbs for four layers hosiery bandage using Velfour bandage. Other 15 patients, Group B, were treated with conventional wound dressing. Velfour and crepe bandage were done once weekly for three weeks. RESULTS: DVT was cause of chronic venous ulcer in 70% patient in group A and in 73.3% in Group B. Majority of patients were having left sided chronic venous ulcers. The mean duration of the ulcers was 15.6 vs 10.86 months (group A vs. group B). At the end of 3rd week, in 55% wounds in Group A were healed except few big and deep wounds remained. Most of these wounds also became smaller with minimal discharge. Size of wounds significantly decreased in Group A vs. Group B patients (0.7±0.81 cm vs. 1.73±0.77 cm, p<0.00031). However, cost of treatment in group A remained higher than group B. CONCLUSIONS: Our study has shown that four layer compressive bandage using Velfour is an easy, effective, and reproducible method of treatment for the chronic venous ulcer.

Identification of Anticancer Peptides from Bovine Milk Proteins and Their Potential Roles in Management of Cancer: A Critical Review.

Cancer is the most widely recognized reason for human deaths globally. Conventional anticancer therapies, including chemotherapy and radiation, are very costly and induce severe side effects on the individual. The discovery of natural anticancer compounds like peptides may thus be a better alternative for cancer prevention and management. The anticancer peptides also exist in the amino acid chain of milk proteins and can be generated during proteolytic activities such as gastrointestinal digestion or food processing including fermentation. This paper presents an exhaustive overview of the contemporary literature on antitumor activities of peptides released from milk proteins. In addition, caseins and whey proteins have been evaluated for anticancer potential using the AntiCP database, a web-based prediction server. Proline and lysine, respectively, dominate at various positions in anticancer peptides obtained from caseins and whey proteins. The remarkable number of potential anticancer peptides revealed milk proteins as favorable candidates for the development of anticancer agents or milk and milk products for reduction of cancer risks. Moreover, anticancer peptides liberated from milk proteins can be identified from fermented dairy products. Although current findings of correlation between dairy food intakes and cancer risks lack consistency, dairy-derived peptides show promise as candidates for cancer therapy. This critical review supports the notion that milk proteins are not only a nutritious part of a normal daily diet but also have potential for prevention and/or management of cancer.

Effect of probiotics on antioxidant and antimutagenic activities of crude peptide extract from yogurt.

Search for bioactive peptides is intensifying because of the risks associated with the use of synthetic therapeutics, thus peptide liberation by lactic acid bacteria and probiotics has received a great focus. However, proteolytic capacity of these bacteria is strain specific. The study was conducted to establish proteolytic activity of Lactobacillus acidophilus (ATCC® 4356™), Lactobacillus casei (ATCC® 393™) and Lactobacillus paracasei subsp. paracasei (ATCC® BAA52™) in yogurt. Crude peptides were separated by high-speed centrifugation and tested for antioxidant and antimutagenic activities. The degree of proteolysis highly correlated with these bioactivities, and its value (11.91%) for samples containing all the cultures was double that of the control. Liberated peptides showed high radical scavenging activities with 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), IC50 1.51 and 1.63mg/ml, respectively and strong antimutagenicity (26.35%). These probiotics enhanced the generation of bioactive peptides and could possibly be commercially applied in new products, or production of novel anticancer peptides.

Large versus Small Dose Magnesium Sulfate Infusion in Tetanus.

INTRODUCTION: Evidence based guidelines regarding the use of magnesium sulfate in tetanus is lacking. Hence, our objective was to compare two infusion doses of magnesium sulfate to control the tetanic spasms. METHODS: Data of 14 adult male patients admitted in the intensive care unit were retrieved. Twelve adult ventilated patients received magnesium infusion as an adjunct to diazepam therapy to control tetanic spasms. We retrospectively divided them into two groups for comparison. Group 1 patients (n=7) received a smaller dose (<1 g.h(-1)) than group 2 (n=5) (1.5 to 2 g.h(-1)). RESULTS: The duration of symptoms before arrival to hospital was significantly longer in group 1 than group 2. The Ablett severity grade was II in three patients in group 1 and III in all patients of group 2. In Ablett severity grade III patients, the diazepam dose used was significantly higher in group 1 (n=4) (292±48 mg.d(-1)) than group 2 (n=3) (106±9 mg.d(-1)) as magnesium infusion dose was restricted due to hypotension in group 1. Amongst the patients who received MgSO(4) for ≥10 days, the requirement of diazepam was significantly reduced in the second week (174.1±59.2 mg/d) than the first week (325.4±105.9 mg.d(-1)) of infusion in group 2 (n=4) but not in group 1 patients (n=4). CONCLUSIONS: The larger dose of MgSO(4) infusion was titrated to control tetanic spasms as an adjunct to diazepam in select group of patients without hypotension. Uncontrolled hypotension, cardiac arrhythmia and renal failure were the factors to limit its infusion dose.

Reoperative characteristics after microfracture of knee cartilage lesions in 454 patients.

PURPOSE: There is only limited information on those patients who fail following microfracture treatment at the knee joint. Evaluation was made of factors associated with treatment failure and clinical outcome assessment among this collective. METHODS: The study included a total of 560 patients who had previously undergone microfracture for the treatment of symptomatic knee joint cartilage lesions. For the remainder of this study, inclusion criteria were patients that underwent reoperation at the initially operated knee joint (index knee) due to symptoms related to the primary site of microfracture intervention (failure patients) with a minimum postoperative follow-up of 2 years. The remaining cohort of patients served as internal control (non-failure patients). Chart reviews were performed to identify patient and defect characteristics. Patients were evaluated for postoperative Lysholm knee scores, Tegner activity scale, as well as preoperative and postoperative numeric analogue scales (NAS) for function and pain (10 = highest possible function, no pain). RESULTS: A total of 454/560 (81.1 %) subjects were completely evaluated. Overall, 123/454 patients (26.9 %) (age at operation 43.9 ± 14.1 years, 56 female, BMI 25.8 ± 3.6, 30 smokers, 61.1 ± 68.3 month symptom duration, postoperative follow-up 5.0 ± 2.1) met the inclusion criteria. The postoperative Lysholm score was 63.0 ± 24.6 and the Tegner score was 4.0; NAS function improved from 2.8 ± 1.8 to 4.8 ± 2.2 (P < 0.001), and NAS pain improved from 3.2 ± 2.1 to 5.0 ± 2.4 (P < 0.001). Exclusively, the overall defect size/knee joint was smaller (P = 0.006), postoperative follow-up was longer (P = 0.002), and existense of previous surgery (77.2 vs. 51.6 %, P < 0.001) was more frequent in failure subjects when comparing to non-failure patients (n = 331). The overall clinical outcome among failure subjects was significantly worse when comparing to non-failure subjects. Regression analysis identified that lower preoperative NAS values, being a smoker, and patello-femoral lesions were associated with a higher probability of reoperation. CONCLUSION: Within the collective presented here, microfracturing was associated with a high frequency of reoperation. Clinical outcome is worse when compared with that of patients without reoperation. Specific parameters can be identified that increase the eventuality of failure following microfracture treatment. LEVEL OF EVIDENCE: IV.

Clinical outcome following the first-line, single lesion microfracture at the knee joint.

CASE SERIES: Level of evidence, 4. BACKGROUND: Arthroscopic microfracture of chondral defects across the knee joint is a frequent treatment modality. There is only limited information on the clinical outcome in patients without previous surgery and single lesions. PURPOSE: Evaluation of clinical outcome following microfracture in patients without previous surgery and single lesions and identification of prognostic factors. METHODS: Inclusion criteria were patients with single-lesion knee joint first-line microfracturing at minimum 2 years postoperatively. Charts were reviewed to identify patient and defect characteristics. Clinical outcome was evaluated by IKDC and Lysholm knee scores, Tegner activity scale and a numeric analogue scale (NAS) for function and pain (10 = highest possible function, no pain). RESULTS: Totally, 145 patients (age at operation 47.92 ± 15.7) met inclusion criteria. Average defect size was 2.7 ± 1.9 cm(2). Postoperatively, IKDC was 73.1 ± 18.5, Lysholm 77.6 ± 19.1, Tegner 4.5 ± 1.7, NAS pain 6.5 ± 2.6 and NAS function 6.4 ± 2.3. Significantly better clinical outcome was observed in male patients than in female patients. Regression analysis including all patient and defect characteristics highlighted that singly the parameter shorter symptom duration (P = 0.018) significantly predicted an improved postoperative clinical outcome. CONCLUSION: Microfracturing results in a satisfying clinical outcome, but no full recovery in patients without previous surgery and single lesions. Specific parameters facilitate outcome prognosis and therefore may aid in indicating surgery.

Nitric oxide signaling modulates cholinergic synaptic input to projection neurons in Drosophila antennal lobes.

Biochemical investigations have demonstrated that nitric oxide synthase (NOS) is distributed widely in the olfactory system. However, little is known about the action of NO at the synaptic level on identified neurons in local circuits that process chemosensory signals. Here, using whole-cell recordings, the effect of NO on cholinergic synaptic input to olfactory projection neurons (PNs) is determined in the Drosophila antennal lobes (ALs), which has become an excellent model for studying early olfactory-processing mechanisms. We found that the NO donor SNP/SNAP or the NO precursor L-arginine significantly decreased the frequency of cholinergic spontaneous excitatory postsynaptic currents (sEPSCs) in PNs. Conversely, soluble guanylyl cyclase (sGC) inhibitor oxadiazolo-quinoxaline-one (ODQ) significantly increased the frequency of cholinergic sEPSCs in PNs. The subsequent application of 8-bromo-cGMP significantly attenuated the effects of ODQ, indicating the possible involvement of NO-cGMP signaling. To determine the role of NO in quantal release of acetylcholine (Ach) to PNs, cholinergic miniature excitatory postsynaptic currents (mEPSCs) were recorded. SNP significantly decreased the frequency of mEPSCs, but exhibited no effect on the amplitude or the decay time constant of mEPSCs in PNs. The effect of SNP on the frequency of mEPSCs could be eliminated by ODQ as well. Thus, these results suggest that elevated NO concentration decreased cholinergic synaptic input to PNs in a sGC-dependent manner. In this way, NO signaling is suited to fulfill a regulatory role to effectively fine-tune network activity in Drosophila ALs.