The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis.

Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.

Patients' perception about risks and benefits of antithrombotic treatment for the prevention of venous thromboembolism (VTE) after orthopedic surgery: a qualitative study.

BACKGROUND: The 9th edition of the American College of Chest Physicians' Antithrombotic Therapy and Prevention of Thrombosis guidelines emphasize the importance of considering the risk-benefit ratio of "patient-important" outcomes. However, little is known about patients' perception and understanding regarding the different outcomes of antithrombotic treatment after orthopedic surgery, and the factors that influence their decision to use these treatments. Using a series of semi-structured interviews, we explored patients' understanding and perception concerning the benefits and risks of antithrombotic treatment for the prevention of venous thromboembolism (VTE) after joint replacement surgery. METHODS: A series of semi-structured interviews were conducted with patients who had undergone knee or hip replacement surgery at a tertiary care hospital (Brigham and Women's Hospital, Boston, MA) in 2014. Discussions were recorded and transcribed. Two investigators independently coded and analyzed the data to identify important themes and concepts using the constant comparative method. RESULTS: Of 64 patients who were invited, 12 patients (19 %) completed the interviews. The majority of patients (92 %) were aware of the benefits of antithrombotic therapy for reducing the risk of blood clots, while less than half of them had a clear understanding of deep vein thrombosis and pulmonary embolism. While all patients were aware of risk of minor bleeding, only 6 patients (50 %) considered the risk of major bleeding as a possible side effect of antithrombotic treatment. Overall, patients perceived bleeding as a less important outcome than a thrombotic event. The lack of awareness about the risk of major bleeding, the assumption that a short-term exposure would not meaningfully affect bleeding risk, and the assumption that bleeding is a controllable event influenced their perception. Most patients (83 %) stated that their decision to use antithrombotic medications was mainly based on the trust in their physician's expertise. CONCLUSIONS: Patients perceived thrombotic events as more important outcomes than bleeding events. Patients' understanding of thrombotic and bleeding events varies and may play a key role in their preferences. The majority of patients stated that trust in their physician's expertise had a large influence on their decision to use antithrombotic medications.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

Primary total hip replacement in childhood, adolescence and young patients: quality and outcome of clinical studies.

OBJECTIVE: The present meta-analysis illustrates relevant information about hip replacement in young patients that has been published during the past 3 decades. MATERIAL AND METHODS: Based on a MedLine literature review a total of 95 studies were evaluated. Parameters for evaluation of study quality and outcome were implant survival rates (ISR),number of patients, indications, follow-up, surgical approaches and number of surgeons. RESULTS: Most studies consider patient numbers <50. In 33 studies one implant system was applied compared to 65 studies in which more than one system was used. Most studies include different surgical approaches. 20% of all studies contained neither the number of surgeons,nor the type of surgical approach. The overall ISR could be evaluated in 67 studies. Sufficient data about the ISR of stem and/or sockets were available in 50 papers. CONCLUSIONS: Most published studies analyzed inhomogeneous study populations; study variables vary as do the implants used for treatment.

The stability of the hip after the use of a proximal femoral endoprosthesis for oncological indications: analysis of variables relating to the patient and the surgical technique.

AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.

Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury.

Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury.

Morbidity and mortality of portal hypertension.

Portal hypertension occurs in several aetiologically distinct disease states associated with either increased flow or increased resistance in the portal venous system. The morbidity and mortality observed are the result of ascites formation, impaired hepatic metabolism, encephalopathy and, most ominously, variceal haemorrhage. Patients with conditions in which there is relatively little hepatic parenchymal damage (non-cirrhotic portal hypertension) tend to have fewer episodes of encephalopathy and are better able to tolerate bleeding episodes than those patients with underlying cirrhosis. Similarly, the development of ascites varies with respect to the aetiology of the portal hypertension. This chapter discusses the natural history of the various disease states that manifest portal hypertension, thus allowing critical evaluation of the various therapeutic modalities used in its treatment.

Cost and effectiveness of routine pathological examination of operative specimens obtained during primary total hip and knee replacement in patients with osteoarthritis.

BACKGROUND: The challenge of cost-efficiency is maintaining the quality of medical care while reducing costs and eliminating unnecessary practices. The purpose of this investigation was to evaluate the cost and effectiveness of routine pathological examination of surgical specimens from patients undergoing primary total hip or knee replacement for the treatment of osteoarthritis. METHODS: Effectiveness was assessed by comparing clinical and pathological diagnoses associated with 1,234 consecutive primary total joint replacements (471 hip and 763 knee replacements) performed between 1992 and 1995 in one hospital in patients with the clinical diagnosis of osteoarthritis. Clinical and pathological diagnoses were considered concordant if they agreed, discrepant if they differed without a resultant change in patient management, and discordant if they differed with a resultant change in patient management. Cost identification was performed by determining charges, reimbursement, and costs in 1998-adjusted American dollars for both total hip and total knee replacement. The cost per health-effect was determined by calculating the cost per discrepant and discordant diagnosis. RESULTS: The prevalence of concordant diagnoses was 97.6 percent (1,205 of 1,234) (95 percent confidence interval, 96.6 to 98.4 percent), the prevalence of discrepant diagnoses was 2.3 percent (twenty-eight of 1,234) (95 percent confidence interval, 1.4 to 3.1 percent), and the prevalence of discordant diagnoses was 0.1 percent (one of 1,234) (95 percent confidence interval, 0.1 to 0.3 percent). The cost per discrepant diagnosis was $4,383, and the cost per discordant diagnosis was $122,728. CONCLUSIONS: Routine pathological examination of surgical specimens from patients undergoing primary total hip or knee replacement because of the clinical diagnosis of osteoarthritis had limited cost-effectiveness at our hospital due to the low prevalence of findings that altered patient management.

Recurrence of giant-cell tumors of the long bones after curettage and packing with cement.

The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement. The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al. (six of sixteen), and those who had not had adjuvant treatment with either a high-speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study.

We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.

The role of stress and mood in sickle cell disease pain: an analysis of daily diary data.

The role of stress and mood in the onset and course of sickle cell disease (SCD) pain was examined using a daily diary design. Fifteen adults with SCD completed daily diaries about their pain, stress, mood, and health care and medication use for an average of 94 days. Multilevel random effects models indicated that stress was significantly and positively related to same-day pain ratings. Stress remained a significant predictor of pain after omitting stressors related to SCD. Mood also showed significant associations with same-day pain in the expected directions. In addition, stress and mood were associated with health care and medication use during painful episodes. Finally, painful episodes were preceded by increases in stress 2 days previously, suggesting that stress may play a role in the onset of SCD pain.

Adolescents' attitudes and experiences regarding levonorgestrel 100 mcg/ethinyl estradiol 20 mcg.

STUDY OBJECTIVE: Oral contraceptive pills (OCs) are a commonly prescribed method of birth control for sexually experienced adolescents. The purpose of the current study was to describe anticipated parental involvement and adolescent compliance with pill taking, and to describe experiences with a 20-mcg OC regarding satisfaction and side effects after six cycles. DESIGN: Anticipated parental involvement and anticipated compliance, and experiences with an OC, were assessed at baseline, and after the first and sixth cycles during a clinical trial of oral contraceptives, which required parental consent. SETTING: Three adolescent medicine clinics in New York, NY; Cincinnati, OH; and San Juan, Puerto Rico. PARTICIPANTS: The sample consisted of 43 female adolescents with a mean age of 17 years. RESULTS: The majority of adolescents living with a parent anticipated parental involvement, and few adolescents anticipated difficulties with consistent pill taking. For two side effects (weight and mood changes), more than 30% of the adolescents anticipated the occurrence or worsening of side effects. However, few adolescents actually experienced increases in any of the nine side effects assessed. Ninety-seven percent of adolescents in this trial reported being satisfied with a 20-mcg OC. CONCLUSIONS: Health care providers can assess adolescents' anticipated difficulties with compliance with daily pill taking, and desire for help from their parents. This information can be incorporated into counseling to promote consistent and correct use.

Colour forms of Amazonian cichlid fish represent reproductively isolated species.

Laboratory mate choice experiments have confirmed species status for cichlid fish in the African Great Lakes that differ in colour and little else. Colour differences between allopatric populations of the South American cichlid genus Apistogramma are known for many species, yet the status of such populations has not been previously tested. Analysis of the genetic relationships and mate choice characteristics of populations previously described as Apistogramma caetei from eastern Amazonia indicates genetic differentiation into at least three allopatric lineages, which also show strong prezygotic isolation through female mate choice, confirming them as Biological species. If future studies confirm that this result is indicative of a general trend, the species richness of the South American cichlid fishes may presently be seriously underestimated.

Coupling of CO2 laser energy into ionized blowoff material.

The fraction of incident laser energy coupled into laser-produced ions has been measured for CO2-TEA laser pulses incident on aluminum surfaces in vacuum. The fraction increases with increasing laser power density, reaching a value of 0.06 at 1.85 X 10(8) W/cm2 .

CLEO 1981.

The Optical Society of America, together with the Institute of Electrical and Electronics Engineers, Quantum Electronics and Applications Society, sponsored the first Conference on Laser and Electrooptics held in Washington, D.C., in June 1981. The 15 May 1982 issue of Applied Optics contains sixteen of the papers presented.

Tumors about the knee in children.

Tumors are rare causes of knee symptoms in children but must be considered in the differential diagnosis of pediatric knee pain in order to avoid errors in treatment that could result in loss of limb or even life. Experience with 199 bone and soft-tissue tumors about the knee in children are reviewed. The majority of lesions were benign bone tumors (n = 101), with osteocartilaginous exostoses, nonossifying fibromas, and chondroblastomas predominating. Malignant bone tumors (n = 59) were less frequent, and osteosarcoma (n = 48) was by far the most common sarcoma. Soft-tissue lesions (n = 31) were much less frequent and included rhabdomyosarcoma, synovial sarcoma, fibrosarcoma, and desmoid tumors. A careful history, physical examination, and review of roentgenograms are essential to avoid errors in diagnosis. Malignant tumors require roentgenograms and laboratory studies in sequence to stage the patient. A properly performed biopsy established the diagnosis in most instances. Popliteal cysts, stress fractures, infection, myositis ossificans, histiocytosis, and other lesions can mimic tumors and delay correct diagnosis.

Optical phase conjugation in Hg1 - xCdxTe.

We have observed phase-conjugate signals at 12, 77, and 295 K in n-type Hg1 - xCdxTe (x = 0.216-0.232) using degenerate four-wave mixing at 10.6 microm. The external power-reflection coefficient increases with the product of pump-power densities and saturates at 9%. The values of the third-order nonlinear susceptibility X(3) derived from these measurements agree with the theory of Wolff and Pearson [Phys. Rev. Lett. 17, 1015 (1966)] for X(3) that is due to conduction-band nonparabolicity.

The effects of ethanol administration on portal pressure and gastroesophageal collateral blood flow in patients with alcoholic cirrhosis.

The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture. Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood-alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic-vein pressure, free hepatic-vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone. Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage.

No evidence of a countercurrent multiplier in the intestinal villus of the dog.

The hypothesis that a countercurrent multiplier within the intestinal villus increases osmolality in the distal villus tip was tested. Total sodium, potassium, and water content of intestinal tissue samples was measured. The results showed no significant difference in the total Na plus K concentration (millimoles per kilogram H2O +/- SEM) between the villi tips (185.1 +/- 7.7), whole villi (179.8 +/- 5.4), or intestine minus villi (177.2 +/- 1.7). In contrast, in the kidney (where the existence of a countercurrent multiplier has been demonstrated), the renal medulla had a total Na plus K concentration of 284 +/- 17.1 that was significantly more than the renal cortical concentration of 163 +/- 3.1. Villous tissue osmolality should be in osmotic equilibrium with intestinal luminal fluid. Sampling of intestinal luminal fluid revealed a total Na plus K concentration of 145-165 mmol/kg H2O, a figure compatible with normal luminal osmolality of 280-320 mosmol/kg H2O. These results deny the existence of a countercurrent multiplier in the intestinal villus of the dog.