Antifungal activity of extracts and purified saponins from the rhizomes of Chamaecostus cuspidatus against Candida and Trichophyton species.

AIM: To evaluate the antifungal activity of extracts of Chamaecostus cuspidatus against Candida and Trichophyton species. METHODS AND RESULTS: Crude ethanol extracts of leaves, stems and rhizomes were prepared and evaluated for antimicrobial activity. Only the rhizomes extract (RE) showed antifungal activity but had no inhibitory effect against bacteria (Staphylococcus aureus and Escherichia coli). The RE was then submitted to liquid-liquid partition with hexane (Hex), dichloromethane, chloroform, ethyl acetate and water. The Hex fraction (Hex Fr) from the RE was found to have the best antifungal effect. Three known saponins were isolated from the Hex Fr, of which two (dioscin and aferoside A) showed good antifungal activity. In addition, Hex Fr and the two bioactive compounds had no antibacterial effect, but exhibited fungicidal activity, caused significant changes in the morphology of the fungal cells and showed anti-Candida albicans biofilm activity. Finally, the bioactive plant products presented greater selectivity for fungal cells over normal human cells. CONCLUSIONS: The rhizomes of C. cuspidatus have bioactive saponins that function as effective antifungals against Candida and Trichophyton species, and have antibiofilm activity against C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: Chamaecostus cuspidatus REs may have potential clinical application towards the management of superficial mycoses caused by Candida and Trichophyton species.

Correlation between SARC-F Score and Ultrasound-Measured Thigh Muscle Thickness in Older Hospitalized Cancer Patients.

BACKGROUND: Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) score is frequently used for screening the sarcopenia risk in older people. However, the agreement between SARC-F and loss of ultrasound-derived muscle thickness in hospitalized older cancer patients is unexplored. OBJECTIVE: The primary objective was to evaluate the relationship between the SARC-F score and ultrasound-derived muscle thickness of rectus femoris and vastus intermedius in older hospitalised cancer patients. The secondary objective was to identify the presence of sarcopenia. MEASUREMENTS: A cross-sectional study enrolled forty-one older hospitalised cancer patients ongoing chemotherapy or surgical treatment. Body weight (kg) was measured using a digital scale and height using a portable stadiometer to assess body mass index. SARC-F was performed to assess and classify sarcopenia risk (with (SARC-F: ≥4), without (SARC-F: <4). US-derived muscle thickness of rectus femoris and vastus intermedius was assessed using a portable ultrasound. Relationship between the SARC-F and muscle thickness was tested using Pearson´s correlation and Bland-Altman analyses. RESULTS: Approximately, 46.3% of the patients presented sarcopenia and a lower non-significant muscle thickness of rectus femoris and vastus intermedius (SARC-F ≥4: 18.54±6.28 vs. SARC-F <4: 22.22±9.16 mm, p=0.07). There was a moderate negative correlation between SARC-F and muscle thickness (r=-0.40, p=0.004). Additionally, Bland-Altman plots no found systematic bias risk between SARC-F and ultrasound-derived muscle thickness. CONCLUSIONS: Approximately, 46.3% of older hospitalized cancer patients presented sarcopenia. Additionally, we found a moderate inverse correlation and no systematic bias risk between SARC-F and ultrasound-measured muscle thickness.

Adult-onset systemic autoinflammatory disorders: a clinical approach.

Autoinflammatory disorders (AIDs) are a subgroup of immune-mediated syndromes that result from a primary dysfunction of the innate immune system. AIDs can be either monogenic or polygenic diseases. Unlike organspecific AIDs, systemic AIDs are characterized by fever and/or elevation of acute-phase reactants. This review aims to describe the most common adult-onset systemic AIDs, focusing mostly on polygenic and mixed-pattern diseases which are expected to be more prevalent in adult patients than monogenic AIDs overall. The literature was searched in Medline database. Organ-specific or childhood-onset systemic AIDs were excluded. AIDs were divided in three distinct groups: mixed-pattern, polygenic and adult-onset monogenic AIDs. Most adult-onset AIDs are polygenic but late-onset disease is not rare among monogenic AIDs such as familial Mediterranean fever (FMF). The diagnosis of systemic AIDs in adults is often delayed due to several factors and sometimes it is only established when amyloidosis or other complications are present. Therefore, it probably makes sense to primarily exclude common AIDs in adult patients with fever of unknown origin (and probably different presentations such as polyserositis) since a high prevalence of adult-onset Still's disease or FMF is usually expected. Colchicine, nonsteroidal anti-inflammatory drugs, steroids, immunosuppressive agents, interleukin-1 inhibitors and tumor necrosis factor antagonists constitute common therapeutic options for systemic AIDs.

A new acridone with antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans.

AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.

Potential drug-drug interactions and polypharmacy in institutionalized elderly patients in a public hospital in Brazil.

WHAT IS KNOWN ON THE SUBJECT?: Older individuals constitute an increasing proportion of the population, and therefore, are the major consumers of drugs. The elderly, especially those with mental disabilities, frequently develop chronic diseases and start using numerous drugs. Drug-drug interactions (DDIs) are a major clinical problem in the elderly population, and previous studies have focused only on antidepressants and others types of drugs used to treat mental health conditions. WHAT THIS ARTICLE ADDS TO EXISTING KNOWLEDGE?: This study shows that in hospitalized elderly patients with mental disorders (aged 60-69 years), polypharmacy (≥5 drugs) and the use of drugs that act on the cardiovascular, respiratory and nervous systems can lead to potential drug-drug interactions. Moreover, it was reported that the prevalence of drug-drug interactions in elderly patients with mental disorders was high during their hospitalization in a public hospital in Brazil. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses should know the factors associated with drug-drug interactions in hospitalized elderly patients with mental disorders to choose appropriate strategies for avoiding treatment failure and adverse events in patients. ABSTRACT: Introduction Despite the impact on patient safety and the fact that prevalence is higher in older patients, previous research did not analyse drug-drug interactions (DDIs) in view of nursing care of elderly psychiatric patients. Aim To identify potential drug-drug interactions and polypharmacy in prescriptions of aged inpatients with psychiatric disorders and analyse associated factors. Methods In this retrospective cross-sectional study, we analysed the medical records of institutionalized patients diagnosed with psychiatric disorders (n = 94), aged >60 years, and prescribed multiple medications. Drug prescriptions were checked at admission, midway through and the last prescription. Factors associated with DDI occurrence were assessed using multivariable logistic regression analysis. Results A DDI prevalence potential of 67.0%, 74.5% and 80.8% occurred in patients at admission, midway through hospitalization and the last prescription, respectively. Most of the prescribed drugs were nervous system agents. A high percentage of serious and contraindicated potential DDIs occurred. Age between 60 and 69 years, use of cardiovascular and respiratory system drugs, and the number of medications contributed significantly to DDI. Implications for mental health nursing Knowledge on the factors associated with DDIs in patients with mental disorders can contribute to the improvement of effectiveness and safety of nursing care.

Attitudes towards suicidal behaviour and associated factors among nursing professionals: A quantitative study.

WHAT IS KNOWN ON THE SUBJECT?: Self-confident health professionals with positive and understanding attitudes can take better care of people with suicidal behaviour, but the factors associated with these attitudes are not known. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The majority of nursing professionals had no experience or training in mental health or suicide. They were less self-confident and had more negative attitudes. Nurses and nursing assistants who worked before in mental health services were more understanding with people with suicidal behaviour. Nurses and nursing assistants who were working in prehospital services were less self-confident to taking care of people with suicidal behaviour. Some members of the nursing team had already seriously considered committing suicide. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The practicing, support and training in mental health may improve the nurses' attitudes and emotional competencies. It is important to know why few nurses had suicide-related training, despite the relevance of this issue. Training in mental health or suicide need to include attitudinal and emotional competencies. It is important to offer emotional support to emergency nursing professionals. ABSTRACT: Background The attitudes towards suicide of emergency nurses may affect the care provided. However, the factors associated with these attitudes remain unclear. Objective To investigate attitudes towards suicidal behaviour and associated factors among nursing professionals working in emergency settings. Methods A cross-sectional observational study including 28 nurses and 118 who were nursing assistants employed at two emergency services in Brazil was conducted. Data were collected in 2015 using a self-administered sociodemographic questionnaire and the Suicide Behavior Attitude Questionnaire (SBAQ). Results The majority of participants reported having no experience or training in mental health or suicide. They reported more negative feelings towards the patient and a lower self-perception of professional competence regarding suicidal behaviours, and these attitudes seemed to reinforce each other. Nurses who worked in mental health services reported less moralistic/judgemental attitudes. Working in prehospital services was associated with having a lower self-perception of professional competence. There were professionals who reported thinking seriously about committing suicide. Conclusion When combined with support and training, practicing mental health nursing may serve as an opportunity to develop favourable attitudes and emotional competences, and these issues need to be addressed in suicide education strategies.

Effect of electrical stunning frequency and current waveform in poultry welfare and meat quality.

This study aimed to evaluate the effects of different stunning frequencies and electrical current waveforms on chicken welfare and meat quality. Two-hundred-thirty-two Cobb broilers, 48 d of age and 2.76 ± 0.47 live-weight, were randomly assigned into 4 stunning treatments - 2 frequencies (300 Hz and 650 Hz) and 2 current waveforms (direct current [DC] and alternating current [AC]). Broilers were electrically stunned in a water bath in a commercial slaughterhouse (70 V, 100 mA). The electronarcosis and stunning efficiency were confirmed by assessment of visual parameters (absence of rhythmic breathing, ocular reflex, and coordinated wing flapping) and blood parameters (lactate, glucose, creatine kinase, sodium, and potassium), which were measured after bleeding. The incidence of traumas and injuries was assessed after plucking. Meat quality analysis was performed in Pectoralis major (PM), with determinations of pH, breast yield (PMY), water holding capacity (WHC), water absorption capacity (WAC), thawing loss (DL), cooking loss (CL), shear force (SF), and instrumental color (a*, b*, L*, C*, and h). The interaction between waveform and frequency was significant (P < 0.05) only for lactate, sodium, and lightness (L*). Lactate and sodium levels decreased at 300 Hz-DC. Meat lightness increased at 300 Hz-DC. The individual effect of frequency was significant for glucose, creatine kinase, potassium, WHC, PMY, b*, C*, and h. Regarding waveform, AC decreased plasma glucose and DC decreased creatine kinase and WAC. In general, stunning frequency exerts greater influence than waveform on the welfare and meat quality parameters of broilers. The use of frequency at 650 Hz proved to render animals efficiently unconscious and to promote greater meat quality.

Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism.

STUDY QUESTION: What is the prevalence and functional consequence of ANOS1 (KAL1) mutations in a group of men with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Three of forty-two (7.1%) patients presented ANOS1 mutations, including a novel splice site mutation leading to exon skipping and a novel contiguous gene deletion associated with ichthyosis. WHAT IS KNOWN ALREADY: CHH is characterized by lack of pubertal development and infertility, due to deficient production, secretion or action of GnRH, and can be associated with anosmia/hyposmia (Kallmann syndrome, KS) or with a normal sense of smell (normosmic CHH). Mutations in the anosmin-1 (ANOS1) gene are responsible for the X-linked recessive form of KS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 42 unrelated men with CHH (20 with KS and 22 with normosmic CHH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were screened for mutations in the ANOS1 gene by DNA sequencing. Identified mutations were further investigated by RT-PCR analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hemizygous mutations were identified in three (7.1%) KS cases: a novel splice acceptor site mutation (c.542-1G>C), leading to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing); a recurrent nonsense mutation (c.571C>T, p.Arg191*); and a novel 4.8 Mb deletion involving ANOS1 and eight other genes (VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X) in KS associated with ichthyosis. LIMITATIONS, REASONS FOR CAUTION: Objective olfactory testing was not performed in all cases of self-reported normosmia and this may have underestimated the olfactory deficits. WIDER IMPLICATIONS OF THE FINDINGS: This study further expands the spectrum of known genetic defects associated with CHH and suggests that patients with self-reported normal olfactory function should not be excluded from ANOS1 genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Portuguese Foundation for Science and Technology. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Results of a round-robin exercise on read-across.

A round-robin exercise was conducted within the CALEIDOS LIFE project. The participants were invited to assess the hazard posed by a substance, applying in silico methods and read-across approaches. The exercise was based on three endpoints: mutagenicity, bioconcentration factor and fish acute toxicity. Nine chemicals were assigned for each endpoint and the participants were invited to complete a specific questionnaire communicating their conclusions. The interesting aspect of this exercise is the justification behind the answers more than the final prediction in itself. Which tools were used? How did the approach selected affect the final answer?

Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.

Systemic sclerosis sine scleroderma: a case report of anterior uveitis.

Systemic sclerosis (SSc) sine scleroderma (ssSSc) is characterized by the absence of skin involvement, despite other manifestations of systemic sclerosis are present. It is not known whether sSSc represents a forme fruste of limited cutaneous SSc or a distinct entity, but the 2013 American College of Rheumatology/European League Against Rheumatism criteria for the classification of SSc have considered SSc without skin involvement to be a distinct subset. The authors present the case of a 70-year old female that was referred for a consultation for Raynaud's phenomenon and a chronic anterior uveitis (CAU). She had a history of dysphagia, diffuse pulmonary emphysema and a biopsy-documented fibrosis of the upper lobes, and an idiopathic non-ischemic dilated cardiomyopathy with severe left ventricle systolic dysfunction and left bundle branch block. Anti-nuclear and anti-centromere antibodies were positive, while manometry revealed distal esophageal hypomotility. After establishing the diagnosis of ssSSc and starting immunosuppression, the ocular disease improved, while the lung and heart diseases remained stable. This case underlines that it is very important to suspect SSc when CAU is present and/or skin thickening is absent. To our knowledge, this is the first report of CAU in a patient with ssSSc.

Accuracy of GPS devices for measuring high-intensity running in field-based team sports.

We compared the accuracy of 2 GPS systems with different sampling rates for the determination of distances covered at high-speed and metabolic power derived from a combination of running speed and acceleration. 8 participants performed 56 bouts of shuttle intermittent running wearing 2 portable GPS devices (SPI-Pro, GPS-5 Hz and MinimaxX, GPS-10 Hz). The GPS systems were compared with a radar system as a criterion measure. The variables investigated were: total distance (TD), high-speed distance (HSR>4.17 m·s(-1)), very high-speed distance (VHSR>5.56 m·s(-1)), mean power (Pmean), high metabolic power (HMP>20 W·kg(-1)) and very high metabolic power (VHMP>25 W·kg(-1)). GPS-5 Hz had low error for TD (2.8%) and Pmean (4.5%), while the errors for the other variables ranged from moderate to high (7.5-23.2%). GPS-10 Hz demonstrated a low error for TD (1.9%), HSR (4.7%), Pmean (2.4%) and HMP (4.5%), whereas the errors for VHSR (10.5%) and VHMP (6.2%) were moderate. In general, GPS accuracy increased with a higher sampling rate, but decreased with increasing speed of movement. Both systems could be used for calculating TD and Pmean, but they cannot be used interchangeably. Only GPS-10 Hz demonstrated a sufficient level of accuracy for quantifying distance covered at higher speeds or time spent at very high power.

The effects of 3,3',4,4'-tetrabromobiphenyl on rats fed diets containing a constant level of copper and varying levels of molybdenum.

Copper (Cu) metabolism is altered in rats fed diets high in molybdenum (Mo) and low in Cu. This 10-week study was carried out to examine the effects of supplemental Mo (7.5-240 µg/g diet) on male Sprague-Dawley rats fed diets adequate in Cu (5 µg/g diet) and to determine the susceptibility of Mo-treated animals to the environmental pollutant 3,3',4,4'-tetrabromobiphenyl (TBB). After 7 weeks of dietary treatment, half of the rats in each group received a single IP injection of TBB (150 µM/kg bw), while the other half received the corn oil vehicle. Rats sacrificed at 10 weeks showed no effects of Mo on growth, feed efficiency, or selected organ or tissue weights. Dose-dependent effects on plasma Mo (0-5.1 µg/mL), plasma Cu (0.95-0.20 µg/mL), and bone Cu (3.4-10 µg/g) in control through the high dose were found. Cu sequestration in the bone of Mo-treated rats is a new finding. TBB treatment resulted in dramatic weight loss and loss of absolute organ mass. Relative organ weights were increased, except for the thymus. TBB altered the concentrations of certain amino acids. Compared to control rats, this polybrominated biphenyl congener significantly decreased plasma Cu and ceruloplasmin at higher concentrations of dietary Mo and promoted the process of plasma Cu decrease by Mo, suggesting a combined effect.

[Peripheral precocious puberty: 46, XY complete gonadal dysgenesis]. / Pubertad precoz periférica: disgenesia gonadal completa 46 XY.

Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases. A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89G> T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma.

Ensino de bem-estar e dor animal em cursos de medicina veterinária no Brasil / Teaching pain and animal welfare in Veterinary Medicine courses in Brazil

Currículos de medicina veterinária devem disponibilizar ferramentas para que os futuros profissionais atendam a demanda da sociedade, que inclui preocupações diretas com os animais. O objetivo deste trabalho foi traçar um perfil do panorama geral do ensino da medicina veterinária em relação a questões de bem-estar e dor animal. O método utilizado foi análise de documentos disponíveis online e coleta de dados via aplicação de questionários para coordenadores de curso de medicina veterinária. A descrição do curso, sua grade curricular e ementário foram estudados. Observou-se que 46% das 94 instituições estudadas apresentavam a disciplina de bem-estar animal e 26% ofereciam a disciplina de etologia. Houve evidência de que há uma pronta relação com a esfera física do bem-estar animal, sendo que as outras duas esferas, comportamental e psicológica, não recebem atenção similar ao longo dos cursos. Na avaliação do ementário, o termo "bem-estar animal" é empregado com caráter difuso e o termo "dor" encontra-se presente em 54% dos cursos estudados, relacionado principalmente a disciplinas de patologia, fisiologia, farmacologia e anestesiologia. Conclui-se que o ensino brasileiro de medicina veterinária enfatiza a esfera física do bem-estar animal, sendo importante o enriquecimento em relação às esferas comportamental e psicológica e ao ensino da dor.

The curricula of veterinary medicine should provide tools for future professionals to meet society demands, which include direct concerns for the animals. The overall scenario of education in veterinary medicine on issues of animal welfare and pain was studied. This study was conducted through the analysis of documents available online and via questionnaires to coordinators of veterinary medicine programs. The program description, its curriculum and course content descriptions were considered. Results show that 46% of the 94 institutions studied offer an animal welfare course and 26% offer an ethology course. We observed a direct relationship with the physical component of animal welfare; the other two components, the behavioral and psychological ones, do not receive similar attention throughout the programs. In the study of course contents of the veterinary programs, the term 'animal welfare' is used in a diffuse manner and the term 'pain' appears in 54% of the programs studied, mainly related to disciplines covering its pathology, physiology, pharmacology and anesthesiology. We conclude that in the teaching of veterinary medicine in Brazil there is an emphasis on the physical realm of animal welfare, and that there is room for improvement in the naturalness and psychological realms and in the teaching of pain.

The synergy of -260T T CD14 and -308GG TNF-α genotypes in survival of critically ill patients.

Literature suggests that the analysis of several polymorphic genetic markers is more informative than the analysis of a single polymorphism. In this study, we tested whether the shared inheritance of TLR2 and TLR4 and TNF-α allelic variants may act in synergy with -260C>T CD14 SNP on the outcome from critical conditions. We monitored 524 critically ill patients from South Brazilian, daily from the ICU admission to their discharge from hospital, or death. Our results revealed that TLR2, TLR4 or TNF-α SNPs alone did not show a significant role in the outcome from critical illness. However, when we performed a combined analysis with the CD14 inheritance, we detected a significant higher survivor rate in -260TT CD14/-308GG TNF-α individuals (P = 0.037). In the adjusted analysis including the main clinical predictors to mortality, we observed that -260TT/-308GG double-genotype was a significant protective factor towards survival (P = 0.046). An increased probability for survival of -260TT/-308GG was also observed by 'pathway genetic load' analysis (unweighted: P = 0.041; weighted: P = 0.036). When we applied a hazard function analysis with the -260TT/-308GG variable as a discriminating factor, -260TT/-308GG patients group had, in fact, a higher survivor rate (P = 0.024). Connected to the beneficial effect of -260TT CD14, the -308GG TNF-α genotype was protective against the reported over expression of TNF-α caused by -308A rare allele. Results support the hypothesis that the interaction between -260C>T CD14 and -308G>A TNF-α functional SNPs may be synergistically influencing the outcome of critically ill patients.

[Lipoatrophic diabetes. A therapeutic challenge]. / Diabetes lipoatrófica. Un reto terapéutico.

Congenital generalised lipodystrophy is a rare autosomal recessive disorder characterised by a marked deficiency of adipose tissue and usually recognised at birth. This disorder is associated with early development of metabolic complications such as hypertriglyceridemia, hepatic steatosis, and insulin resistance. These complications ultimately lead to fatal events as a consequence of early atherosclerosis, lipoatrophic diabetes and hepatic cirrhosis. The authors report the case of a patient diagnosed, based on clinical and laboratory findings, in the first year of life. The established diagnosis was then confirmed by identifying a mutation in the BSCL2 gene. Because the hypertriglyceridemia and diabetes were refractory to treatment, the authors present this case in order to reflect on the best therapeutic management of this pathology.

[Pseudohypoparathyroidism type Ia - a novel mutation]. / Seudohipoparatiroidismo tipo Ia. Una mutación original.

Pseudohypoparathyroidism Ia (PHP-Ia) results from a specific deficiency of the alpha subunit of stimulatory G protein, manifested by resistance to parathormone and a characteristic phenotype, referred to as Albright hereditary osteodystrophy (AHO). Several mutations were identified in the GNAS1 gene in individuals with PHP-Ia and pseudopseudohypoparathyroidism (PPHP). A single GNAS1 mutation may be responsible for both PHP-Ia e PPHP in the same family, when inherited from the maternal and the paternal allele, respectively. The authors present the case of a teenage boy with PHP- Ia. The study revealed the GNAS1 mutation c.899A >T (p.Lys300Ile) in exon 11. After the genetic study of his parents, we have identified the same mutation in the mother, who had only somatic alterations (AHO), not associated with hormone resistance (PPHP). This is an original mutation, not yet described in the literature.