Adeno-associated viral serotypes differentially transduce inhibitory neurons within the rat amygdala.

Recombinant adeno-associated viruses (AAV) are frequently used to make localized genetic manipulations within the rodent brain. It is accepted that the different viral serotypes possess differing affinities for particular cell types, but it is not clear how these properties affect their ability to transduce specific neuronal cell sub-types. Here, we examined ten AAV serotypes for their ability to transduce neurons within the rat basal and lateral nuclei of the amygdala (BLA) and the central nucleus of the amygdala (CeA). AAV2 based viral genomes designed to express either green fluorescent protein (GFP) from a glutamate decarboxylase (GAD65) promoter or the far-red fluorescent protein (E2-Crimson) from a phosphate-activated glutaminase (PAG) promoter were created and pseudotyped as AAV2/1, AAV2/4, AAV2/5, AAV2/6, AAV2/7, AAV 2/8, AAV2/9, AAV2/rh10, AAV2/DJ and AAV2/DJ8. These viruses were infused into the BLA and CeA at equal titers and twenty-one days later tissue within the amygdala was examined for viral transduction efficiency. These serotypes transduced neurons with similar efficiency, except for AAV4 and AAV5, which exhibited significantly less efficient neuronal transduction. Notably, AAV4 and AAV5 possess the most divergent capsid protein sequences compared to the other commonly available serotypes. We found that the Gad65-GFP virus did not exclusively express GFP within inhibitory neurons, as assessed by fluorescent in situ hybridization (FISH), but when this virus was used to transduce CeA neurons, the majority of the neurons that expressed GFP were in fact inhibitory neurons and this was likely due to the fact that this nucleus contains a very high percentage of inhibitory neurons.

Infrared and Raman screening of seized novel psychoactive substances: a large scale study of >200 samples.

The potential of IR absorption and Raman spectroscopy for rapid identification of novel psychoactive substances (NPS) has been tested using a set of 221 unsorted seized samples suspected of containing NPS. Both IR and Raman spectra showed large variation between the different sub-classifications of NPS and smaller, but still distinguishable, differences between closely related compounds within the same class. In initial tests, screening the samples using spectral searching against a limited reference library allowed only 41% of the samples to be fully identified. The limiting factor in the identification was the large number of active compounds in the seized samples for which no reference vibrational data were available in the libraries rather than poor spectral quality. Therefore, when 33 of these compounds were independently identified by NMR and mass spectrometry and their spectra used to extend the libraries, the percentage of samples identified by IR and Raman screening alone increased to 76%, with only 7% of samples having no identifiable constituents. This study, which is the largest of its type ever carried out, therefore demonstrates that this approach of detecting non-matching samples and then identifying them using standard analytical methods has considerable potential in NPS screening since it allows rapid identification of the constituents of the majority of street quality samples. Only one complete feedback cycle was carried out in this study but there is clearly the potential to carry out continuous identification/updating when this system is used in operational settings.

Surface-enhanced Raman spectroscopy of novel psychoactive substances using polymer-stabilized Ag nanoparticle aggregates.

A set of seized "legal high" samples and pure novel psychoactive substances have been examined by surface-enhanced Raman spectroscopy using polymer-stabilized Ag nanoparticle (Poly-SERS) films. The films both quenched fluorescence in bulk samples and allowed identification of µg quantities of drugs collected with wet swabs from contaminated surfaces.

Isolation and structural determination of non-racemic tertiary cathinone derivatives.

The racemic tertiary cathinones N,N-dimethylcathinone (1), N,N-diethylcathinone (2) and 2-(1-pyrrolidinyl)-propiophenone (3) have been prepared in reasonable yield and characterized using NMR and mass spectroscopy. HPLC indicates that these compounds are isolated as the anticipated racemic mixture. These can then be co-crystallized with (+)-O,O'-di-p-toluoyl-D-tartaric, (+)-O,O'-dibenzoyl-D-tartaric and (−)-O,O'-dibenzoyl-L-tartaric acids giving the single enantiomers S and R respectively of 1, 2 and 3, in the presence of sodium hydroxide through a dynamic kinetic resolution. X-ray structural determination confirmed the enantioselectivity. The free amines could be obtained following basification and extraction. In methanol these are reasonably stable for the period of several hours, and their identity was confirmed by HPLC and CD spectroscopy.

Shared decision-making in back pain consultations: an illusion or reality?

PURPOSE: Amid a political agenda for patient-centred healthcare, shared decision-making is reported to substantially improve patient experience, adherence to treatment and health outcomes. However, observational studies have shown that shared decision-making is rarely implemented in practice. The purpose of this study was to measure the prevalence of shared decision-making in clinical encounters involving physiotherapists and patients with back pain. METHOD: Eighty outpatient encounters (comprising 40 h of data) were observed audio-recorded, transcribed verbatim and analysed using the 12-item OPTION scale. The higher the score, the greater is the shared decision-making competency of the clinicians. RESULTS: The mean OPTION score was 24.0% (range 10.4-43.8%). CONCLUSION: Shared decision-making was under-developed in the observed back pain consultations. Clinicians' strong desire to treat acted as a barrier to shared decision-making and further work should focus on when and how it can be implemented.

Accumulation and effects of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) exposure in the green anole (Anolis carolinensis).

Environmental contamination by energetic compounds is an increasing international concern, although little is known of their accumulation in and affect on wildlife. Reptiles are often good models for contaminants studies due to natural history traits that increase their potential for exposure. We report a study to assess accumulation and effects of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX, High Melting Explosive) in green anoles (Anolis carolinensis). Acute oral toxicity (LD(50)) was estimated to exceed 2000 mg/kg body weight in adult male and female anoles using a standard up-and-down method. Accumulation of HMX was assessed in adult females via dietary exposure and into eggs by two routes (directly from the soil and via maternal transfer). HMX readily accumulated into adult females in a dose-dependent manner and into eggs following both exposure pathways. However, total HMX in soil-exposed eggs was up to 40-times greater than those exposed via maternal transfer. Although there was a suggestion of an HMX-induced reduction in body weight in adult females, overall there were no effects observed over the 12 week exposure period. The only significant effect on eggs was a 50% reduction in hatching success for eggs exposed to 2000 mg/kg HMX in the soil during incubation. Growth and survival of hatchlings was not affected by HMX exposure. Our results demonstrate that HMX accumulates through the food chain and into eggs from the soil, but likely poses minimal threat to lizards except to hatching success in eggs incubated in soils with HMX levels near maximum environmental concentrations.

Primary care utilization patterns before and after lung cancer diagnosis.

The objective of this study was to evaluate change in primary care utilization rates after lung cancer diagnosis in the Veterans Health Administration. We used electronic medical record data (1997-2005) to identify male veterans (n = 323) with incident lung cancers. Primary care utilization rates were assessed in the 12-month period before and after cancer diagnosis. Statistical analysis included paired t-tests. Rates of primary care utilization decreased by 0.02 visits per person-month (VPPM) in the 12-month period after cancer diagnosis (P > 0.05). Utilization for acute conditions decreased by 20% (P < 0.01) in the 12-month period after diagnosis, from 0.32 VPPM before diagnosis to 0.12 VPPM after diagnosis. Utilization for chronic conditions remained stable after diagnosis (0.29 VPPM vs. 0.29 VPPM, P > 0.05). Indications for primary care utilization after diagnosis were similar to indications for utilization prior to diagnosis. Common indications for utilization included hypertension and lower respiratory infections. We speculate that primary care utilization for acute conditions was lower after cancer diagnosis because several of the acute conditions (e.g. upper respiratory infection) treated prior to the cancer may have been harbingers of the cancer diagnosis. Additional research is required to illuminate how primary care can best be delivered during the initial phase of cancer treatment.

Carcinoid syndrome.

As clinical awareness increases, carcinoid is becoming increasingly identified, often at an earlier stage in the course of the disease. However, many patients remain undiagnosed until well into the late stages of the illness, at the time when their carcinoid syndrome becomes apparent. This review examines contemporary methods of detecting and assessing advanced carcinoid disease, and then continues to discuss strategies (both potentially curative and palliative) to control symptoms, and both prolong and improve quality of life for these patients.

AIDS-defining opportunistic illnesses in the HAART era in New York City.

Despite widespread availability of HAART, opportunistic illnesses (OIs) still occur and result in an increased risk of mortality among persons with AIDS. We estimated the incidence of OIs among all new adult AIDS cases in New York City in 2000 overall and in demographic and clinical subgroups and identified factors associated with occurrence of an AIDS-defining OI versus AIDS diagnosis based on low CD4+ values only. In 2000, 5,451 new AIDS cases were reported to the New York City Department of Health and Mental Hygiene. Of these 27.4% (95% CI: 22.8-32.6) had at least one OI, most frequent being Pneumocystis jiroveci pneumonia (12.2%) and M. tuberculosis (5.3%); 47.1% (41.7-52.5) had a late HIV diagnosis (i.e.< or =6 months before AIDS diagnosis). Persons with a late HIV diagnosis not in recent care had a 3.5-fold increased odds (1.29-9.63) of an OI, compared to non-late testers in care. Other predictors of an OI were injection drug use and older age. We conclude that OIs remain prevalent in the HAART era and late testers not in care are especially likely to develop an OI. Our results support comprehensive HIV programs promoting early HIV testing and linkage to care to prevent OI-related morbidity and mortality.

Management of the multiple limb amputee.

ISSUE: Multiple limb amputations involving at least one upper extremity are very uncommon. The amputation of both an upper and lower limb is even more uncommon. Due to the rarity of these amputations therapists are uncertain regarding the most appropriate treatment methods. While the majority of the protocols used for single limb amputations are appropriate for these multiple limb amputees, there are differences. Loss of multiple limbs creates a problem of overheating for the individual. Loss of an arm and leg results in difficulty donning the prostheses and difficulty using crutches and parallel bars during mobilization. METHOD: A review is given of 16 multiple limb amputees seen in our rehabilitation centre in the last 15 years. Return to work was seen in one third and was not related to the number of the amputations. A higher proportion of these multiple limb amputations occur through alcoholism or attempted suicide behaviour than occurs with either single upper limb amputations or lower limb amputations. This existing behaviour can create a management problem for the rehabilitation team during rehabilitation. CONCLUSION: Guidelines as to appropriate prosthetic and preprosthetic care are provided to assist the practitioner who has the acute and long term care of these patients. All multiple limb amputees should be referred to a specialized rehabilitation centre to discuss prosthetic options and long term rehabilitation requirements. This paper does not discuss bilateral lower limb amputations when not combined with an upper limb amputation.

Inter-observer reliability of clinical outcome measures in a lower limb amputee population.

PURPOSE: In an attempt to find a more clinically useful functional outcome measure specifically tailored for lower limb amputees undergoing inpatient prosthetic rehabilitation, a 6-month prospective assessment of inter-rater reliability for Harold Wood-Stanmore Mobility Scale Data, including two handicap scales, was undertaken. An analysis of the data is presented in this paper. METHODS: An inter-rater reliability study was undertaken using four observers to complete admission and discharge scores for the three disability/handicap scales on 14 consecutive patients over 6 months. RESULTS: The disability mobility scale demonstrated perfect observer agreement on admission and at discharge the inter-rater reliability for this measure was high (0.83). By contrast, reliability between observers for admission scores on the handicap mobility scale was poor at 0.49 but reasonably high on discharge (0.83). On admission, inter-rater reliability for handicap physical independence was very low (0.15). At discharge, reliability improved to 0.69 being more consistent with results achieved for the other axes. CONCLUSIONS: This study confirms the good inter-rater reliability demonstrated previously in the literature but reveals poor inter-rater reliability for the two handicap scales. The latter will require modification before they can be used with confidence in conjunction with the disability scale.

Save that arm: a study of problems in the remaining arm of unilateral upper limb amputees.

A study has been made by questionnaire, personal examination and telephone interview of unilateral upper limb amputees seen at the Prince Henry Hospital, Australia between 1994 and 1997. There were 60 questionnaires posted. Replies were received from 46. Problems were noted in the remaining arm of 23 (50%). The respondents' problems not only consisted of overuse symptoms, but also of an exacerbation of pre-existing arthritis and injury due to trauma to the remaining arm during the accident. Case histories are given in 3 typical cases. Treating professionals are warned about the hazards that one arm amputations present to the remaining arm.

Congenital toxoplasmosis: prenatal diagnosis, treatment and postnatal outcome.

We report a female patient with congenital toxoplasmosis who presented with hydrops fetalis and cerebral abnormalities, detected on fetal ultrasound. Following prenatal treatment, the hydrops fetalis resolved and at four months of age she has normal growth and development. This case emphasizes the potential good prognosis in cases with congenital toxoplasmosis detected and treated prenatally.

Allegations of sexual misconduct: a risk management perspective.

Increasingly, patients are making complaints to state licensing boards and filing lawsuits against healthcare providers alleging sexual misconduct. This article addresses the risk management implications of patient allegations of sexual misconduct involving inappropriate touching by healthcare providers during an examination or treatment. From a risk management standpoint, techniques can be implemented before and after these incidents that can help reduce the facility's exposure.

Painful neuromata following upper limb amputation.

Painful neuromata occurring after upper limb amputation are a significant cause of stump pain and limit the success of prosthetic training and use. There is little information in the literature regarding incidence, consequences or outcomes of painful neuromata subsequent to upper limb amputation. This article reports an analysis of thirty-two consecutive upper limb amputees. Of these 25% had moderate-to-severe stump pain and clinical signs suggestive of neuromata. All patients with neuromata were limited in their ability to use a prosthesis prior to surgery and following failure of conservative measures, were referred for surgical opinion. Six patients have undergone surgical management. The results of surgery, with respect to pain and prosthetic usage, are discussed.

The long-term outcome of upper limb amputees treated at a rehabilitation centre in Sydney, Australia.

A follow-up study by questionnaire or interview has been made of the 27 respondents of 41 upper limb amputees (66%) treated at the Royal South Sydney Hospital between 1981 and 1990. Prosthetic use of 8 h/day or more was 37% and occasional use was 18.5%. The prosthetic users were more likely to be distal amputees. The reason for the low level of prosthetic use is not known. The majority of non-users discarded prostheses after leaving their rehabilitation programme. Occupational changes were made by 72% of the amputees. The unemployment rate at follow-up was similar to the rest of the community, which is a better outcome than 25 years ago. Activities of daily living had been affected in all patients, but to a lesser extent in prosthetic users. Leisure pursuits were changed in 70% of patients, with these activities being more sedentary and indoor in nature. Of the 18 car drivers, 15 drove automatic cars with modifications. Phantom pain was experienced by 16 of the respondents (59%) and stump pain was experienced by seven. Only 26% used medication or alcohol for the pain. Pain did not affect prosthetic use or functional ability.

Rehabilitation after a letter-bomb attack causing bilateral hand loss and other injuries: case report.

The rehabilitation of patients after terrorist attacks has received scant attention in the literature. A case is reported of a patient injured in a letter-bomb explosion; his injuries were bilateral hand loss, loss of one eye, and perforated ear-drums. The successful rehabilitation of this patient to normal work in 8 months is described. A rehabilitation plan for management of similar patients is given.