Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.

BACKGROUND: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup. AIM: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children. PATIENTS AND METHODS: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected. RESULTS: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children. CONCLUSION: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child.

Effects of feeding 25-hydroxyvitamin D3 with an acidogenic diet during the prepartum period in dairy cows: Mineral metabolism, energy balance, and lactation performance of Holstein dairy cows.

Our objective was to determine the effects of feeding 25-hydroxyvitamin D3 [25(OH)D3], or vitamin D3 (cholecalciferol) on plasma, mineral, and metabolite concentrations, mineral balance, mineral excretion, rumination, energy balance, and milk production of dairy cows. We hypothesized that supplementing 3 mg/d of 25(OH)D3 during the prepartum period would be more effective than supplementing vitamin D3 at the National Research Council (2001) levels to minimize calcium imbalance during the transition period and improve milk production of dairy cows. Forty multiparous, pregnant nonlactating-Holstein cows were enrolled in this study. Body weight, body condition score, parity, and milk yield in the previous lactation (mean ± standard deviation) were 661 ± 59.2, 3.46 ± 0.35, 1.79 ± 0.87, and 33.2 ± 6.43 kg/d, respectively. Cows were enrolled into the blocks (n = 20 for each treatment) at 30 d of the expected day of calving to receive an acidogenic diet (373 g/kg of neutral detergent fiber and 136 g/kg of crude protein, dry matter basis; -110 mEq/kg) associated with the treatments: (1) control (CTRL), vitamin D3 at 0.625 mg/d (equivalent to 25,000 IU of vitamin D3/d) or (2) 25(OH)D3 at 3 mg/d (equivalent to 120,000 IU of vitamin D3/d). All cows were fed with the base ration for 49 d after calving. Blood samples were taken on d 7, 0, 1, 2, 21, and 42, relative to calving. No effect of treatment was observed for prepartum dry matter intake or body condition score. A trend for increase of ionized Ca was observed for the cows fed 25(OH)D3, compared with the CTRL, but no effect of treatment was detected for total Ca or total P. Feeding 25(OH)D3 increased colostrum yield. The plasmatic concentration of 25-hydroxyvitamin D3 was increased with 25(OH)D3 supplementation. 25-Hydroxyvitamin D3 supplementation increased plasma glucose concentration at parturition. The postpartum dry matter intake was not influenced by treatments. Feeding 25(OH)D3 increases milk yield, 3.5% fat-corrected milk, and energy-corrected milk and improves milk yield components in early lactation. Overall, these findings suggest that 25(OH)D3 at 3 mg/d can improve the energy metabolism and lactation performance, compared with the current-feeding practice of supplementing vitamin D3 at 0.625 mg/d.

Effects of restricted vs. step up dietary adaptation for 6 or 9 days on feedlot performance, feeding behaviour, ruminal and blood variables of Nellore cattle.

This study was designed to determine effects of quantitatively restricted intake of the final finishing diet as a means of dietary adaptation compared with diets increasing in concentrate (step up) over periods of 6 and 9 days on feedlot performance, carcass characteristics, feeding behaviour, blood gas profile and rumen morphometrics of Nellore cattle. One hundred twenty 22-month-old Nellore bulls (352 ± 20 kg) were randomly allocated in 24 pens and fed for 84 days. The experimental design was a completely randomized block with 2 × 2 factorial arrangement of treatments: adaptation using either step up protocol for 6 days or 9 days or restriction protocol for 6 days or 9 days, where the pen (five bullocks/pen; six pens/treatment) was considered the experimental unit. Cattle adapted by step up protocol had significantly greater average daily gain throughout the study when compared to those adapted by restriction protocol, regardless of adaptation length. During the adaptation period, a greater dry matter intake fluctuation was observed for animals maintained on restriction programme when compared to those adapted to the finishing diets using step up protocol. In addition, a protocol × length interaction for rumenitis scores was observed, where the level of injuries to the ruminal wall was significantly higher for the cattle adapted by restriction protocol for 9 days and lower for animals submitted for 9 days to the step up programme. Likewise, a protocol × length interaction for mitotic index was observed, in which cattle adapted by step up protocol for 9 days had lower numbers of cells in mitosis. Thus, the step up protocol led to better feedlot performance, and based on this fact, the length of 9 days promoted better rumen epithelium adaptation of Nellore cattle to high-concentrate diets.

Use of site symmetry in supercell models of defective crystals: polarons in CeO2.

In supercell calculations of defective crystals, it is common to place a point defect or vacancy in the atomic position with the highest possible point symmetry. Then, the initial atomic structure is often arbitrary distorted before its optimization, which searches for the total energy minimum. In this paper, we suggest an alternative approach to the application of supercell models and show that it is necessary to preliminarily analyze the site symmetry of the split Wyckoff positions of the perfect crystal supercell atoms (which will be substituted or removed in defective crystals) and then perform supercell calculations with point defects for different possible site symmetries, to find the energetically most favorable defect configuration, which does not necessarily correspond to the highest site symmetry. Using CeO2 as an example, it is demonstrated that this use of the site symmetry of the removed oxygen atoms in the supercells with vacancies allows us to obtain all the possible atomic and magnetic polaron configurations, and predict which vacancy positions correspond to the lowest formation energies associated with small polarons. We give a simple symmetry based explanation for the existence of controversies in the literature on the nature of the oxygen vacancies in CeO2. In particular, the experimentally observed small polaron formation could arise for oxygen vacancies with the lowest Cs site symmetry, which exist in 3 × 3 × 3 and larger supercells. The results of first principles calculations using a linear combination of atomic orbitals and hybrid exchange-correlation functionals are compared with those from previous studies, obtained using a widely used DFT+U approach.

Experimental evidence of shock wave measurements with low-velocity (<100 m s-1) and fast dynamics (<10 ns) capabilities using a coupled photonic Doppler velocimetry (PDV) and triature velocity interferometer system for any reflector (VISAR) diagnostic.

We present a series of shock-wave measurements on aluminum based on the use of a simultaneous Photon Doppler Velocimetry (PDV) and triature velocity interferometer system for any reflector. Our dual setup can accurately measure shock velocities, especially in the low-speed range (<100 m s-1) and fast dynamics (<10 ns) where measurements are critical in terms of resolution and unfolding techniques. Especially, the direct comparison of both techniques at the same measurement point helps the physicist in determining coherent settings for the short time Fourier transform analysis of the PDV, providing increased reliability of the velocity measurement with a global resolution of few m s-1 in velocity and few ns FWHM in time. The advantages of such coupled velocimetry measurements are discussed, as well as new opportunities in dynamic materials science and applications.

Feedlot performance and rumen morphometrics of Nellore cattle adapted to high-concentrate diets over periods of 6, 9, 14 and 21 days.

The energy content of finishing diets offered to feedlot cattle may vary across countries. We assumed that the lower is the energy content of the finishing diet, the shorter can be the adaptation period to high-concentrate diets without negatively impacting rumen health while still improving feedlot performance. This study was designed to determine the effects of adaptation periods of 6, 9, 14 and 21 days on feedlot performance, feeding behaviour, blood gas profile, carcass characteristics and rumen morphometrics of Nellore cattle. The experiment was designed as a completely randomised block, replicated 6 times, in which 96 20-month-old yearling Nellore bulls (391.1 ± 30.9 kg) were fed in 24 pens (4 animals/pen) according to the adaptation period adopted: 6, 9, 14 or 21 days. The adaptation diets contained 70%, 75% and 80.5% concentrate, and the finishing diet contained 86% concentrate. After adaptation, one animal per pen was slaughtered (n = 24) for rumen morphometric evaluations and the remaining 72 animals were harvested after 88 days on feed. Orthogonal contrasts were used to assess linear, quadratic and cubic relationships between days of adaptation and the dependent variable. Overall, as days of adaptation increased, final BW (P = 0.06), average daily gain (ADG) (P = 0.07), hot carcass weight (P = 0.04) and gain to feed ratio (G : F) (P = 0.07) were affected quadratically, in which yearling bulls adapted by 14 days presented greater final BW, ADG, hot carcass weight and improved G : F. No significant (P > 0.10) days of adaptation effect was observed for any of feeding behaviour variables. As days of adaptation increased, the absorptive surface area of the rumen was affected cubically, where yearling bulls adapted by 14 days presented greater absorptive surface area (P = 0.03). Thus, Nellore yearling bulls should be adapted by 14 days because it led to improved feedlot performance and greater development of rumen epithelium without increasing rumenitis scores.

Effect of single nucleotide polymorphisms of CAPN1 and CAST genes on meat traits in Nellore beef cattle (Bos indicus) and in their crosses with Bos taurus.

The objectives of this work were to study the segregation of single nucleotide polymorphisms of the calpain 1, large subunit (CAPN1) and calpastatin (CAST) genes in Nellore (Bos indicus) and Nellore xBos taurus beef cattle, as well as to evaluate their effects on meat traits. For this, 300 animals, including 114 Nellore, 67 Angus x Nellore, 44 Rubia Gallega x Nellore, 41 Canchim, 19 Brangus three-way crosses and 15 Braunvieh three-way crosses, were genotyped for the CAPN4751 [AF_248054.2:g.6545C>T (GenBank accession AF248054.2)] and CAST/DdeI [AF_159246.1:g.2959A>G (GenBank accession AF159246.1)] polymorphisms and phenotyped for Ribeye Area, Backfat Thickness, Intramuscular Fat, Shear Force (SF) and Myofibrillar Fragmentation Index (MFI). In relation to the CAPN4751 polymorphism, a frequency of 10.5% was observed for the C allele in the Nellore breed. In the total sample of studied animals, a significant association was found between genotypes and meat tenderness, assessed by SF (P = 0.005) and MFI (P = 0.008), with genotype CT being more favourable than TT. For the CAST/DdeI polymorphism, a frequency of 55.7% was found for the A allele in the Nellore breed. In the total sample, a significant association was observed between genotypes and meat tenderness - SF (P = 0.004) and MFI (P = 0.006), with genotype AA being more favourable than AG. The relationship between genotypes and aged meat tenderness in confluence with the distribution of favourable alleles shows great potential for application of the CAPN4751 and CAST/DdeI polymorphisms in the genetic improvement of the Nellore breed, whilst contributing to the validation, in this breed and in its crosses with B. taurus, of the association results previously described in the literature.

Gender ratio trends over time in multiple sclerosis patients from Argentina.

Several studies in multiple sclerosis (MS) suggest a trend of increasing disease frequency in women during the last decades. A direct comparison of gender ratio trends among MS populations from Argentina remains to be carried out. The objective of the study was to compare gender ratio trends, over a 50-year span in MS populations from Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients with definite MS with birth years ranging from 1940 to 1989 were included. Gender ratios were calculated by five decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the Argentinean national registry of births. The F/M ratios were calculated using a multivariate logistic regression per five decades by the year of birth approach. Analyses were performed using Stata 10.1. RESULTS: 1069 patients were included. Gender ratios showed a significant increase from the first to the last decade in the whole MS sample (from 1.8 to 2.7; p value for trend=0.023). The Gender ratio did not show differences considering MS subtype. CONCLUSION: our study showed a modest increase of the F/M ratio (from 1.8 to 2.7) over time among patients affected by MS in Argentina.

Intensive care unit management of fulminant hepatic failure.

OBJECTIVE: The aim of this open/retrospective study was to evaluate the outcomes of intensive care unit patients treated for fulminant hepatic failure (FHF) for predictive indices. METHODS: All patients were recovered in the intensive care units with a diagnosis of FHF. We considered three groups of patients: (1) survivors, deceased, and transplanted. SUBJECTS: All patients were fully screened, including liver function indices such as AST, ALT, total and bound bilirubin, albumin and pre-albumin, factors 5 and 7, alpha fetal protein (alpha-PP), other coagulation tests (PT, aPTT, INR, ATIII), and renal function (BUN and creatinine) parameters. For each patient Apache II score was calculated upon admission to the intensive care unit. RESULTS: Apache II score showed efficacy. alpha-PP increased in both surviving and deceased, but not in the transplanted group. After intensive care unit admission, AST and ALT peaks were higher in the deceased DP than in the transplanted group. The INR value at the third day after ICU admission improved in the survivors compared with the other two cohorts. Factor 5 levels were lower among patients undergoing transplantation, but increased in the other two groups. The prognosis was strictly dependent upon the development of renal failure. CONCLUSION: The Apache II score was a sensitive predictive index for outcome. alpha-PP and factor 5 were not related to outcome, but useful for decision making when determining potential liver transplantation. INR can be used as a prognostic index. Intensive treatment beforehand is of primary importance to prevent multiple organ failure.

Relationships of feedlot performance, feeding behavior, rumen morphometrics, and carcass characteristics of Nellore cattle differing in phenotypic residual feed intake.

The objective of this study was to examine the relationship of DMI fluctuation, feedlot performance, feeding behavior, rumen morphometrics, and carcass characteristics in Nellore cattle classified by residual feed intake (RFI). One experiment was conducted in 2 consecutive years using individual pens (1.0 × 7.0 m) at the São Paulo State University feedlot, Dracena campus, Brazil. The experiment in year 1 started in June of 2012 with forty-eight 20-mo-old Nellore yearling bulls with an initial BW of 358.2 ± 19.4 kg. The experiment in year 2 started in January of 2013 with sixty 20-mo-old Nellore yearling bulls with an initial BW of 402.5 ± 33.0 kg. Experiments in years 1 and 2 lasted 94 and 84 d, respectively. All yearling bulls were categorized as high RFI (>0.5 SD above the mean, = 25), medium RFI (±0.5 SD from the mean, = 56), and low RFI (<0.5 SD below the mean, = 27). Visual appraisal to collect behavior data was made on d 40 (finishing period) of both years. Yearling bulls were harvested when average across treatment groups achieved a fat thickness of 4 mm at the 12th rib. Low-RFI yearling bulls had lower daily DMI, expressed either in kilograms ( < 0.01) or as percentage of BW ( < 0.01), and improved G:F ( < 0.01) when compared to high-RFI animals. No differences were observed ( > 0.10) for ADG, final BW, or HCW among RFI groups. Also, low-RFI yearling bulls had thinner final 12th rib ( < 0.01) and biceps femoris (P8) fat thickness ( < 0.01). Low-RFI yearling bulls were slower to consume ( = 0.03) and ruminate ( < 0.01) 1 kg of either DM or NDF. No significant ( > 0.10) RFI effect was observed for any ruminal morphometrics variables evaluated, with the exception of papillae area, in which low-RFI Nellore yearling bulls tended to have smaller ( = 0.07) papillae area than medium-RFI animals. In general, low-RFI Nellore yearling bulls consumed more particles larger than 19 and 8 mm and had a similar performance when compared to both medium- and high-RFI bulls; however, carcass fat composition was negatively impacted.

Disease onset in familial and sporadic multiple sclerosis in Argentina.

UNLABELLED: The present study was carried out to assess if there is an anticipation of age at onset in younger generations of familial multiple sclerosis (FMS) vs. sporadic MS (SMS) in Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients were considered as FMS if they had in their family at least one relative of first or second degree diagnosed with MS; otherwise, patients were considered to have SMS. We compared the age at onset between familial and sporadic cases as well as the age at onset between relatives from different generations in FMS vs. SMS. RESULTS: 1333 patients were included, 97 of them were FMS (7.3%). A lower age at onset in the younger generations of FMS cases was found compared with older generations of FMS as well as. SMS cases (24.1±3.7 years vs. 30.3±5.7 years, and 32.4±9.4 respectively; p<0.001). No differences were observed between older generations of FMS vs. SMS cases (p=0.12). CONCLUSION: we observed an anticipation of age at onset of MS in younger generations of patients with FMS vs. older generations of FMS and SMS.

Effects of feeding a spray-dried multivalent polyclonal antibody preparation on feedlot performance, feeding behavior, carcass characteristics, rumenitis, and blood gas profile of Brangus and Nellore yearling bulls.

The objective of this study was to evaluate the effects of replacing monensin (MON) with a spray-dried multivalent polyclonal antibody preparation (PAP) against several ruminal microorganisms on feedlot performance, carcass characteristics, feeding behavior, blood gas profile, and the rumenitis incidence of Brangus and Nellore yearling bulls. The study was designed as a completely randomized design with a 2 × 2 factorial arrangement, replicated 6 times (4 bulls per pen and a total of 24 pens), in which bulls ( = 48) of each biotype were fed diets containing either MON fed at 300 mg/d or PAP fed at 3 g/d. No significant feed additive main effects were observed for ADG ( = 0.27), G:F ( = 0.28), HCW ( = 0.99), or dressing percentage ( = 0.80). However, bulls receiving PAP had greater DMI ( = 0.02) and larger ( = 0.02) final LM area as well as greater ( < 0.01) blood concentrations of bicarbonate and base excess in the extracellular fluid than bulls receiving MON. Brangus bulls had greater ( < 0.01) ADG and DMI expressed in kilograms, final BW, heavier HCW, and larger initial and final LM area than Nellore bulls. However, Nellore bulls had greater daily DMI fluctuation ( < 0.01), expressed as a percentage, and greater incidence of rumenitis ( = 0.05) than Brangus bulls. In addition, Brangus bulls had greater ( < 0.01) DMI per meal and also presented lower ( < 0.01) DM and NDF rumination rates when compared with Nellore bulls. Significant interactions ( < 0.05) between biotype and feed additive were observed for SFA, unsaturated fatty acids (UFA), MUFA, and PUFA concentrations in adipose tissues. When Nellore bulls were fed PAP, fat had greater ( < 0.05) SFA and PUFA contents but less ( < 0.01) UFA and MUFA than Nellore bulls receiving MON. For Brangus bulls, MON led to greater ( < 0.05) SFA and PUFA and less ( < 0.05) UFA and MUFA than Brangus bulls fed PAP. Feeding a spray-dried PAP led to similar feedlot performance compared with that when feeding MON. Spray-dried PAP might provide a new technology alternative to ionophores.

Treatment of colloid cysts of the third ventricle by aspiration in stereotactic conditions.

Two cases of colloid cysts of the third ventricle are reported. The etiology, clinical symptoms and radiological diagnosis of such lesions are briefly discussed. CT-guided stereotactic aspiration of the cyst's content was performed, with good results in both cases. CT-scan controls performed one year later showed that refilling of the cysts did not occur. The advantages of the technique are described. Review of the literature showed another 17 cases successfully treated by means of stereotactic aspiration. The reliability of this approach is supported by the good outcome and the long follow-up of cases previously reported by other Authors. In our opinion, stereotactic aspiration should thus be the first step in the management of colloid cysts.

Septum pellucidum oligodendroglioma. Case report and review of literature.

Neoplasms of septum pellucidum are rare. Only 124 cases have been published to which we must add the present case report. The literature is concerned with subependymomas and glioblastomas in most cases; there are only 13 cases of oligodendrogliomas. Surgical removal was performed in about 60 cases. This report presents one case of oligodendroglioma of the septum pellucidum which was surgically removed; it demonstrates the peculiar angiographic features of this kind of tumor, stresses the importance of CT scan in the determination of the possibility of surgical removal and finally discusses the therapeutic problems involved.

Hemispheric cavernous angiomas: presumptive preoperative diagnosis.

Clinical history, CT scan and angiography may lead to a correct preoperative diagnosis of hemispheric cavernous angiomas. Surgical results and follow-up are favorable; considering the bleeding risk we think the operation to be mandatory.

Temporary clipping in the surgery of endocranial aneurysms.

The authors' experience in the routine use of temporary clipping procedures in the surgery of endocranial aneurysms is reported. To analyse the validity of such a method we compared the outcome in a series of 153 aneurysms operated according to the traditional procedure (temporary clipping of the afferent vessel only in the case of intraoperative rupture of the aneurysmatic sac) with that of a more recent series of 225 in which the procedure was applied routinely. An unsatisfactory surgical outcome was found in 12.5% and 6.6% of patients respectively, with a corresponding unfavourable outcome in 5.6% and 2.6%.

[Pseudoxanthoma elasticum. A rare cause of upper digestive hemorrhage]. / Pseudoxantoma elastico. Rara causa di emorragia digestiva alta.

Pseudoxanthoma Elasticum (PXE) is a rare inherited elastic tissue disorder with degeneration of elastic fibres involving mainly skin, eyes and the cardiovascular system. Upper gastro-intestinal hemorrhage occurs in 13% of cases and is often resistant to non-surgical methods of treatment. One case report involving recurrent gastric hemorrhage in a young patient with PXE and treated with total gastrectomy is presented. Diagnosis was made, after surgery, by biopsy of skin lesions of the neck. The characteristics of PXE are reviewed and the case is discussed.

[Rupture of the duodenum caused by closed abdominal trauma]. / Rottura di duodeno da trauma addominale chiuso.

A duodenal lesion due to blunt abdominal trauma is an infrequent eventi which makes important diagnostic and therapeutic problems. The preoperative diagnosis is not always easy, especially with retroperitoneal lesion or in injured patients. A plain abdominal radiography or a duodenal radiography with soluble contrast medium helps to achieve a proper diagnosis. Prognosis strictly depends on time between injury and surgical procedures. We report two successfully treated lesions of fourth duodenal due to a blunt abdominal trauma.

[Giant diverticulum of the duodenum. Case report]. / Diverticolo gigante del duodeno. Caso clinico.

The authors describe the case of a 49-year-old man with a giant diverticulum of the duodenum, with apparently scarce symptoms, pointed out by gastroscopy and X-ray of the upper gastrointestinal duct with barium meal. The removal of the lesion, obtained after surgical operation, showed a diverticulum with a 6 cm diameter, with signs of diverticulitis; the histological test did not point out is degenerative lesions. A survey of the recent literature on the matter is presented.

[Hemangiopericytoma of the petrous bone. Considerations apropos of 5 surgically treated cases]. / Les hémangiopéricytomes du rocher. Considérations à propos de 5 cas opérés.

5 cases of infratentorial hemangiopericytomas involving petrous bone are described. They show significant tendency to invade and destroy the bony base reaching into the soft parapharyngeal tissue of the neck. Radiography, tomography and CT scan of the skull demonstrate a large erosion of the petrous bone. At CT scan the lesion appears slightly hyperdense with marked enhancement. Selective angiography shows an important vascular supply from the external carotid artery, the deep and ascending cervical arteries and the extracranial part of the vertebral artery. Embolisation or surgical occlusion of the branches of external carotid artery and cervical arteries are useful to reduce bleeding during biopsy. Radiotherapy is advisable.