Critical reflections on the concept and impact of "scaling up" in Global Mental Health.

The field of Global Mental Health (GMH) aims to address the global burden of mental illness by focusing on closing the "treatment gap" faced by many low- and middle-income countries (LMICs). To increase access to services, GMH prioritizes "scaling up" mental health services, primarily advocating for the export of Western centred and developed biomedical and psychosocial "evidence-based" approaches to the Global South. While this emphasis on scalability has resulted in the increased availability of mental health services in some LMICs, there have been few critical discussions of this strategy. This commentary critically appraises the scalability of GMH by questioning the validity and sustainability of its approach. We argue that the current approach emphasizes the development of mental health services and interventions in "silos," focusing on the treatment of mental illnesses at the exclusion of a holistic and contextualized approach to people's needs. We also question the opportunities that the current approach to GMH offers for the growth of mental health programmes of local NGOs and investigate the potential pitfalls that scalability may have on NGOs' impact and ability to innovate. This commentary argues that any "scaling up" of mental health services must place sustainability at the core of its mission by favouring the growth and development of local solutions and wider forms of support that prioritize social inclusion and long-lasting mental health recovery.

Effects of the transient receptor potential vanilloid 1 antagonist A-425619 on body temperature and thermoregulation in the rat.

Transient receptor potential vanilloid 1 (TRPV1) receptor antagonists have gained much attention for their potential to treat inflammatory and neuropathic pain. However, systemic administration of TRPV1 antagonists induces a period of hyperthermia, a potential liability for small molecule development. Here we characterize the effects of the TRPV1 antagonist A-425619 on body temperature (T(b)) in the rat when administered: (1) alone at different times of the circadian cycle, (2) as repeated hourly or daily treatment, (3) as pre-treatment to prevent capsaicin-induced hypothermia, (4) to capsaicin-desensitized animals, and (5) prior to a heat challenge. Changes in T(b) were compared with compound exposure data, locomotor activity, and time course of efficacy in inflammatory pain models. Without affecting locomotor activity, oral administration of A-425619 induced a transient period of hyperthermia that was followed by a period of hypothermia, a profile unique among reported TRPV1 antagonists. Repeated hourly administration of A-425619 produced an increase in T(b) similar to a single administration. A-425619 had no effect on T(b) when administered to capsaicin-desensitized rats. The duration of A-425619-induced hyperthermia, but not hypothermia, was dependent on the time of the circadian cycle when administered. Pre-treatment with A-425619 attenuated capsaicin-induced hypothermia and did not potentiate T(b) or alter thermoregulatory behavioral responses during a heat challenge. These results indicate that A-425619-induced hyperthermia is transient, circadian-dependent, not related to exposure levels, locomotor activity, or time course of analgesic action, and does not affect the ability to thermoregulate during a heat challenge.

Assessing the impact of nutrient enrichment in estuaries: susceptibility to eutrophication.

The main aim of this study was to develop a generic tool for assessing risks and impacts of nutrient enrichment in estuaries. A simple model was developed to predict the magnitude of primary production by phytoplankton in different estuaries from nutrient input (total available nitrogen and/or phosphorus) and to determine likely trophic status. In the model, primary production is strongly influenced by water residence times and relative light regimes. The model indicates that estuaries with low and moderate light levels are the least likely to show a biological response to nutrient inputs. Estuaries with a good light regime are likely to be sensitive to nutrient enrichment, and to show similar responses, mediated only by site-specific geomorphological features. Nixon's scale was used to describe the relative trophic status of estuaries, and to set nutrient and chlorophyll thresholds for assessing trophic status. Estuaries identified as being eutrophic may not show any signs of eutrophication. Additional attributes need to be considered to assess negative impacts. Here, likely detriment to the oxygen regime was considered, but is most applicable to areas of restricted exchange. Factors which limit phytoplankton growth under high nutrient conditions (water residence times and/or light availability) may favour the growth of other primary producers, such as macrophytes, which may have a negative impact on other biological communities. The assessment tool was developed for estuaries in England and Wales, based on a simple 3-category typology determined by geomorphology and relative light levels. Nixon's scale needs to be validated for estuaries in England and Wales, once more data are available on light levels and primary production.

Allergenicity assessment of apple cultivars: hurdles in quantifying labile fruit allergens.

BACKGROUND: Assessment of allergenicity of foods is important for allergic consumers and regulators. Immunoassays to measure major food allergens are widely applied, often giving variable results. Using the major apple allergen Mal d 1 as a model, we aimed to establish at the molecular level why different immunoassays for assessing allergenicity of apple cultivars produce conflicting outcomes. METHODS: Mal d 1 was measured in 53 cultivars from Italy and 35 from The Netherlands, using four different immunoassays. Purified Mal d 1 standards were molecularly characterized by size-exclusion chromatography (SEC) and mass spectrometry (MS). RESULTS: Three immunoassays using an identical standard gave similar results. Minor differences in sample preparation already resulted in significant loss of allergenicity. The fourth assay, using a different Mal d 1 standard, gave 10- to 100-fold lower outcomes. By SEC, this standard was shown to be almost fully aggregated. This aggregation was accompanied by a decrease of the mass of the Mal d 1 molecule by approximately 1 kDa as analyzed by MS. The deviating immunoassay was shown to selectively recognize this aggregated form of Mal d 1, whereas the other three assays, including the one based on IgE antibody recognition, preferentially bound non-aggregated allergen. CONCLUSIONS: Variable and poorly controllable major allergen modification in both extracts and standards hamper accurate allergenicity assessments of fruits.

An evaluation of germinating beans as a source of vitamin C in refugee foods.

OBJECTIVE: To assess whether germinating pulses and beans are a potential source of vitamin C in rations for refugee communities with poor vitamin C status. DESIGN: High pressure liquid chromatographic assessment of vitamin C content of a range of legumes following germination in light and dark and after cooking. RESULTS: Many species of pulses produced significant quantities of vitamin C up to five days following germination in both light and dark although cooking caused a marked loss of ascorbate. CONCLUSION: Germination of approximately half of the seeds of the pulse constituents of many basic rations would be likely to generate, within a 3-5 d germination period, sufficient ascorbate to provide the 10 mg needed to protect adults against the development of scurvy.

Pregnancy using spermatozoa aspirated from the vas deferens in a patient with ejaculatory failure due to spinal injury.

Aspiration of the vas deferens under local anaesthesia was carried out in a man with ejaculatory failure due to tetraplegia after rectal electrostimulation had failed to provide an ejaculate satisfactory for use in in-vitro fertilization. After passage through a discontinuous Percoll gradient and exposure to 3 mmol pentoxifylline and 3 mmol 2-deoxyadenosine, the final preparation consisted of 50,000 spermatozoa with 4% progressive motility. This was sufficient for the insemination of seven of the 23 oocytes that were collected from the patient's wife by transvaginal ultrasound-guided follicular aspiration. Three high-grade embryos were produced which were transferred transcervically into the uterus 2 days later. A singleton pregnancy resulted which is currently ongoing at 30 weeks gestation. Aspiration of the vas deferens is a relatively simple technique which provides an acceptable alternative to rectal electrostimulation, artificial sperm reservoirs and donor insemination in patients with ejaculatory failure.

Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients.

The effects of sustained pectin ingestion on gastric emptying, glucose tolerance, and hormone responses were studied in 12 stable, non-insulin-dependent (type 2) diabetic patients. Patients were placed on a 2400 kcal, low-fiber (3 g) diet for 2 wk, followed by 4 wk of an isocaloric diet supplemented with 20 g apple pectin/d. Gastric-emptying half-time, plasma glucose, glucagon, and human pancreatic polypeptide levels were determined. Gastric-emptying half-time was prolonged 43% (p less than 0.025) by pectin supplementation and returned to normal 3 d after its discontinuation. Fiber supplementation decreased the incremental area under the glucose tolerance curve from 34.8 +/- 3.0 to 27.9 +/- 3.2 mmol/L (p less than 0.01) but did not affect hormonal responses to a meal. Sustained pectin ingestion slowed the gastric-emptying rate and improved glucose tolerance; however, a direct relationship could not be demonstrated between changes in gastric emptying and changes in the incremental area under the glucose curve (r = 0.22).

Effects of dietary copper, cadmium, iron, molybdenum and manganese on selenium utilization by the rat.

The possible antagonistic effects of different dietary concentrations of copper (1.3-200 mg/kg), cadmium (1-5 mg/kg), iron (20-500 mg/kg), molybdenum (0.3-50 mg/kg) and manganese (0.2-200 mg/kg) on selenium utilization by the rat were studied by the measurement of the absorption and organ distribution of dietary selenium as [75Se]selenite and by effects on organ glutathione peroxidase (GSH-Px: EC 1.11.1.9) activity. Although a high concentration of copper (200 mg/kg) in the diet did not alter the percentage absorption and total-body retention of doses of 75SeO3(2)- by rats, after such treatment tissue 75Se distribution was changed and was lower total selenium in some tissues. After copper treatment (200 mg/kg diet) GSH-Px activity of liver, testis, kidney and whole blood was also lower. Dietary cadmium, iron, molybdenum and manganese at the concentrations investigated had no significant effects on selenium metabolism. Thus it is unlikely that copper, cadmium, iron, molybdenum and manganese at normal dietary concentrations will have a major effect on selenium metabolism in the rat, especially if adequate amounts of selenium are being consumed.

The effects of dietary sulfur on selenium utilization by the rat.

The antagonistic effects of S on Se utilization were studied by measurement of tissue Se concentrations and glutathione peroxidase (GSHpx, E.C.1.11.1.9) activities in rats offered Torula yeast-based diets supplemented with sodium sulfate to provide 1.5, 3, or 5 g S/kg diet. Increasing sulfur concentrations in the diet caused small but significant decreases in GSHpx activity of liver, spleen, heart, lung small intestine, and skeletal muscle. Also significantly decreased were Se concentrations in liver and hair. Dietary sulfur content had no significant effect on body weight gain of the rats. With an adequate supply of Se in the diet, there are probably no major deleterious effects of dietary S on Se metabolism in the rat.

Thiomolybdates in rumen contents and rumen cultures.

Examination of direct and (Cu)-difference spectra of i) the aqueous supernatants of in vitro cultures of bovine rumen contents incubated with MoO42- and potential sources of S2- and ii) samples drawn directly from the rumen of animals receiving high Mo diets yielded evidence of the presence of thiomolybdates. Only MoS42- was detected in the soluble phase of in vitro cultures. Although intense and variable background absorbance precluded full characterization of thiomolybdate species in samples drawn directly from the rumen, both spectral data and the biochemical and clinical responses of animals given high Mo diets were consistent with the conclusion that MoS42- rather than MoOS32- was the predominant thiomolybdate species present in the aqueous phase. Addition of Ca2+ either to rumen cultures before incubation or as a supplement to diets high in MoO42- content inhibited the appearance of MoS42- in the aqueous phase. Evidence of the sequestration of MoS42- and MoOS32- by particulate or microbial fractions of rumen contents is considered in relation to the inhibitory action of Mo upon Cu absorption by ruminants.

Effects of tetrathiotungstate and dithiotungstate on copper metabolism in rats.

The effects of dietary supplementation with ammonium tetrathiotungstate and dithiotungstate on copper metabolism in young rats have been investigated. The addition of WS4(2-) (4-32 mg W/kg diet) decreased growth rates and induced clinical and biochemical signs of Cu deficiency. These were overcome by increasing the dietary content of Cu. The intestinal absorption of 64Cu was impaired and the tissue distribution of absorbed Cu modified by the administration of WS4(2-). No clinical or biochemical defects indicative of Cu deficiency developed in rats receiving WO2S2(2-) in their diet at concentrations up to 32 mg W/kg. In contrast, this oxythioanion enhanced the content of Cu in plasma liver and kidney, especially when dietary Cu was increased. Most of the additional Cu retained by plasma and kidney was associated with albumin and metallothionein, respectively. The effects of these W sources are compared with those caused by their thio- and oxythiomolybdate analogs and are discussed in relation to the mechanisms whereby Mo induces Cy deficiency in ruminants.

Glutathione peroxidase activity and erythrocyte stability in calves differing in selenium and vitamin E status.

1. Glutatione peroxidase activity (EC 1.11.1.9) and erythrocyte stability were measured in Friesian bull calves which were given for 36 weeks semi-purified diets either adequate or low in selenium or vitamin E or both. 2. Dietary Se or vitamin E content had no effect on growth rate and haematlogical values. None of the calves exhibited clinical deficiency symptoms and serum aspartate amino transferase (EC 2.6.1.1) and creatine phosphokinase (EC 2.7.3.2) activities remained normal. Heart and skeletal muscles of all calves appeared macroscopically and microscopically normal ato autopsy. 3. Glutathione peroxidase activity in plasma, blood and other tissues, except the testis, was significantly lower in calves receiving low dietary Se but was independent of dietary vitamin E content. 4. Plasma vitamin E levels decreased rapidly and to very low levels in calves given low vitamin E diets irrespective of the Se content of the diet. 5. A low dietary vitamin E intake increased the susceptibility of erythrocytes to auto- and peroxidative haemolysis whereas a low Se intake in the presence of adequate vitamin E did not. However, erythrocytes from calves receiving low Se and low vitamin E were more susceptible to peroxidative haemolysis than erythrocytes from calves receiving low vitamin E and adequate Se. The effect of dietary vitamin E content on osmotic haemolysis induced by hypotonic saline was variable. 6. The results suggest that measurement of blood glutathione peroxidase activity and the susceptibility of erythrocytes to auto- or peroxidative haemolysis could be used for the differential diagnosis of subclinical Se and vitamin E deficiency in ruminants.

The outcome of surgical treatment as related to the response of the serum albumin level to nutritional support.

Selected nutritional parameters were studied in critically ill surgical patients maintained by parenteral-enteral nutritional support to delineate the nutritional deficits and relate the course of these patients to the nutritional status. Twenty-one of 34 patients had albumin levels of less than 3.5 grams per cent upon admission, and the albumin levels decreased even further after admission. The patients with traumatic injuries had the greatest loss in body weight and urinary nitrogen excretion. Although such large numbers of these patients had depressed serum albumin levels, the survivors were able to increase the serum albumin level to 3.5 grams per cent with intense nutritional support, whereas those not surviving such support were not able to increase the serum albumin level. The response of the serum albumin level to nutritional support is a good indicator as to the same factors preventing survival and effective use of the nutritional elements.

Nutritional deficiencies and nutritional support therapy in geriatric cancer patients.

Nutritional deficits and their correction were studied in 45 cancer patients (age range, 60--86 years) who were undergoing various modalities of cancer therapy. Their nutritional status was maintained with a variety of commercially available special diets, and serum albumin concentrations were sequentially determined in order to gauge the efficacy of the nutritional support. Serum albumin levels were preserved when nutritional support was employed in surgical therapy. However, patients undergoing palliative chemotherapy or radiotherapy responded only to adequate levels of the standard hospital diet with or without supplements of special enteral diets. In the survivors, albumin levels were maintained; in the nonsurvivors, albumin levels decreased. This group of older patients tolerated nutritional support therapy, especially when it was carefully monitored. Satisfactory nutritional therapy can be achieved by use of appropriate enteral formulas. The method lends itself to adequate management in the outpatient or nursing-home situation during certain phases of cancer.