SLC13A5/NaCT is a sodium-coupled citrate transporter expressed in the plasma membrane of the liver, testis, and brain. In these tissues, SLC13A5 has important functions in the synthesis of fatty acids, cholesterol, and neurotransmitters. In recent years, patients homozygous for recessive mutations in SLC13A5, known as SLC13A5 deficiency [early infantile epileptic encephalopathy-25 (EIEE-25)], exhibit severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting tooth development. Although the pathogenesis of SLC13A5 deficiency remains not clearly understood, cytoplasmic citrate deficits, decreased energy status in neurons, and citrate-zinc chelation are hypothesized to explain the neurological deficits. However, no study has examined the possibility of specific pharmacological drugs and/or lifestyle changes synergizing with heterozygosity of SLC13A5 deficiency to increase the risk of EIEE-25 clinical phenotype. Here, we report on a heterozygous SLC13A5-deficient patient who demonstrated evidence of pharmaco-synergistic heterozygosity upon administration of metformin, valproic acid, and starvation. The report illustrates the importance of careful consideration of the potential adverse effects of specific pharmacological treatments in patients with heterozygosity for disease-causing recessive mutations in SLC13A5.

In Europe REACH framework directive imposes data acquisition concerning toxicity on acquatic species before the commercialization of chemicals to assess environmental risks. According to official methods, exposure tests are performed under in vitro and standardized conditions: OECD\'s guideline rules external variables such as water type, feeding conditions, and exposure time. As consequence, such obtained results could be different from effects observed in natural environments. This study collects effects within 24-96 h of exposure to nano metal-oxides (ZnO, TiO2) on D. magna obtained by the exposure under standard OECD conditions comparing them with results obtained by the exposure under more similar conditions to natural environment (i.e. mixture, feeding). High doses exposure determines gas-bubble disease. Animals exposed to LC10 actively ingest nanoparticles under both fasting and feeding conditions. Furthermore, body burial by a coat of nanoparticles thicker in mixtures than in single dispersions was recorded. Furthermore, results show that: (i) effects increase over time; (ii) n-ZnO results less effective than n-TiO2 in both single dispersion, and mixture; (iii) the presence of surfactant increases toxicity of nanoparticles; (iv) immobilization is a more sensitive endpoint than mortality; (v) feeding increases test sensitiveness improving differences among treated and controls till 96 h and allowing longer exposure times than standard OECD test. As general remark, this study provides evidence that in vitro ecotoxicological results obtained under standardized OECD conditions could be significant different to animals\' responses under natural (feeding and mixtures) exposure conditions.

Torture, which violates human rights, is still being practiced worldwide despite of all the bound rules and regulations. Although \"beating\" is the commonest method applied, other physical, psychological and sexual methods are often being practiced. 1975 Tokyo declaration defines torture and the doctor\'s role in managing torture. Injury identification and accurate dating are major challenges faced by medical professionals in dealing with cases of torture. Inadequacy of the history and late presentation are another major issues that often interfere with proper medico-legal management. It would be wise for the professional who is involved in management of torture cases to be thorough of \'Istanbul protocol\' which contain the first set of internationally recognized standards for effective examination of torture victim. This case report discusses some of the entities such as beating, water torture, mock execution and other psychological methods, and rear occurrence of hanging with near death experience.

BACKGROUND: In the 1978 Ireland v. the United Kingdom case, the European Court of Human Rights (ECtHR) did not consider that the so called \"five techniques\" caused enough severity to be considered torture. The intentionality criterion, outlined in the Convention against Torture\'s definition of torture, was also not fully considered. The Istanbul Protocol, which is critical for evidencing torture, did not exist at that time. Although a re-opening of the case was requested in 2014 by Ireland, forensic documentation using the Istanbul Protocol was not used; in 2018, the ECtHR decided against re-opening the case.
OBJECTIVE: By using the Ireland v. The United Kingdom case, this paper aims to map the origins of the five techniques, review whether applying them constitutes torture, analyze the information about the claimants available 30 years later, and explore the ramifications of the ECtHR decision not to revise its judgment.
METHODS: Relevant texts were gathered from the HUDOC database, Cambridge University Press, Wiley Online Library, SCOPUS and MEDLINE /PubMed, and the Library of the ECtHR in Strasbourg.
CONCLUSIONS: The five techniques, elaborated upon in the case of Ireland v. the United Kingdom, were used well before the incidents in Northern Ireland in 1971 and there is evidence that United Kingdom officials have, subsequently, used the techniques. Furthermore, there is clear evidence that the \"Hooded Men\" had cognitive, psychological and neurovegetative symptoms as a result of the five techniques, which had long-term effects. The ECtHR did not take this into consideration when it decided not to re-open the case and the full implications of this decision for future cases and victims remain to be seen.

OBJECTIVE: To determine the ability of sheep to mobilise their body reserves after being deprived of feed prior to transport for slaughter.
METHODS: A total of 240 3- and 4-year-old cull ewes were held off pasture for 0, 9, 18 or 30 hours (n=60 per group) then transported 1 hour by road, unloaded and washed, held in lairage for 3 hours then slaughtered. Blood samples were collected from a subsample of 60 unfasted ewes 1 week earlier, and from all ewes at exsanguination to determine concentrations of serum metabolites indicative of adaptation to fasting. In addition, several attributes of carcass quality were measured.
RESULTS: At slaughter, increased time off pasture prior to transport resulted in no change in glucose concentrations in serum (p=0.140). There were differences (p<0.001) between the group fasted for 30 compared with 0 hours in mean concentrations of free fatty acids (0.98 (SD 0.32) vs. 0.58 (SD 0.23) mmol/L), β-hydroxybutyrate (0.69 (SD 0.17) vs. 0.42 (SD 0.11) mmol/L), triglycerides (0.29 (min 0.13, max 0.83) vs. 0.22 (min 0.06, max 0.96) mmol/L) and urea (10.17 (SD 1.80) vs. 6.94 (SD 2.03) mmol/L). Different periods of feed deprivation had no effect (p>0.05) on carcass weights (mean 22.7, min 13.2, max 32.9 kg) or dressing out percentages (mean 40.9, min 27, max 49%). Meat ultimate pH was unaffected (p>0.05) by the period of feed deprivation but meat became darker (p<0.05) and had reduced redness (p<0.001) with increasing time off feed.
CONCLUSIONS: The results suggest that sheep in variable body condition adapted to the periods of feed deprivation by mobilising their energy reserves without any evidence of metabolic depletion (e.g. depleted blood glucose or high meat pH). However, being deprived of feed they probably experience a degree of hunger.

Commonly used normalization approaches for quantitative reverse transcription polymerase chain reaction analyses include (a) input nucleic acids standardization (ΔC (q) method), (b) normalizing target gene transcript abundance against a single internal reference gene (ΔΔC (q) method), and (c) geometric averaging of multiple reference gene abundance using the geNorm software. We compared these three approaches to examine expression of a negative muscle growth regulator gene, myostatin-I (mstn-I), in the finfish Lates calcarifer, following 4 weeks of nutritional fasting. Interestingly, these three different approaches led to widely divergent data interpretations. When ΔC (q) and subsequently ΔΔC (q) with α-tub as the reference gene were applied to mstn-I expression data, an ∼threefold upregulation of this gene was observed in fasted compared to fed fish. In contrast, mstn-I appeared unchanged when data was normalized against the geometric average of the two apparently most \"stable\" reference genes (elongation factor-1 α (ef1-α) and rpl8) selected from a panel comprising seven commonly utilized candidate reference genes (18S, cat-D, ef1-α, rpl8, gapdh, ubq, and α-tub). The geNorm software erroneously suggested that ef1-α, rpl8, and ubq were the most \"stable\" reference genes, whereas ΔC (q) analysis revealed these genes simply to exhibit similar patterns of regulation in response to fasting. The ΔC (q) approach showed that α-tub was the least variable in its expression level between fasted and fed fish after 4 weeks. The present study also highlights the importance of validating internal references for each time point under investigation when applying ΔΔC (q) and suggests that the more cost-effective ΔC (q) normalization approach, if carefully applied, may in fact produce the most biologically valid results.

Therese Neumann, from Konnersreuth in Bavaria, developed stigmata at the age of 29 and allegedly lived without any food for 36 years. After a fire accident in 1918, she suffered from paralysis, deafness, and blindness. Later she developed stigmata on her extremities and left side of the thorax, bleeding lesions in the skin, bleeding in the eye region, and altered states of consciousness in the form of \"visions\" of religious content. On the basis of a report by her physician, Dr. Otto Seidl, to the Bishopric Ordinariate of Regensburg (1927) and a manuscript for presentation before the Catholic Medical Society of the Netherlands (1928) Seidl had no doubt of the authenticity of these phenomena, and he diagnosed hysteria. While under surveillance by four nuns for 14 days, Neumann exhibited no intake of nourishment; weight measurements and urine tests however suggest the opposite. Investigation in a clinic was refused. Her case is interpreted here in the light of contemporary psychiatry. As far as medical records go, Therese Neumann\'s is one of a series of surprisingly similar cases of stigmata development, conversion disorder, and alleged absence of nutrition. In nosological terms, these would be classified today as dissociative disorders.

BACKGROUND: Brazil reports almost 80% of all leprosy cases in the Americas. This study aimed to identify socioeconomic, environmental, and behavioural factors associated with risk of leprosy occurrence in the endemic North-eastern region.
METHODS: A case-control study in four municipalities.
METHODS: cases of leprosy diagnosed in the previous 2 years, with no other known, current, or past case of leprosy in the household or in the neighbourhood.
METHODS: individuals presenting for reasons other than skin problems to the health unit where the case was diagnosed and who lived in the same municipality as the case with whom it was matched. For each case four controls were selected. A semi-structured questionnaire was used to collect demographic, socioeconomic, environmental, and behavioural data. A multivariate hierarchical analysis was performed according to a previously defined framework.
RESULTS: 226 cases and 857 controls were examined. Low education level, ever having experienced food shortage, bathing weekly in open water bodies (creek, river and/or lake) 10 years previously, and a low frequency of changing bed linen or hammock (>or=biweekly) currently were all significantly associated with leprosy. Having a BCG vaccination scar was found to be a highly significant protective factor.
CONCLUSIONS: Except for BCG vaccination, variables that remained significant in the hierarchical analysis are cultural or linked to poverty. They may act on different levels of the transmission of Mycobacterium leprae and/or the progress from infection to disease. These findings give credit to the hypothesis that person-to-person is not the only form of M. leprae transmission, and that indirect transmission might occur, and other reservoirs should exist outside the human body.

We have proposed that normal food intake is geared toward optimizing the internal milieu for reproduction, despite some components of this milieu being detrimental to health. In dietary restriction, the animal is prevented from eating enough to attain or maintain reproductive capacity and this particular milieu does not materialize. Life extension occurs as a by-product. This idea provides a framework for exploring biomolecular changes in dietary restriction and their relevance to aging. Leptin is a case in point: here, a decrease in leptin level in dietary restriction is explored in the light of leptin\'s role in the complex signaling system of reproductive switch.

This article has, so far, explored the phenomenon of aspiration associated with obstetric general anaesthesia (see Part 1). Part 2 examines the literature pertaining to the history of dietary regimes for labour and the physiological and psychological effect of restricting or allowing food and fluids during labour. The increasing trend among some health professionals to allow food and fluids during labour and research conducted to investigate the effect of the labouring woman\'s oral intake on the labour and birth outcomes is also discussed.