Randomization Procedures for Changing Criterion Designs.

To strengthen the scientific credibility arguments for single-case intervention studies, randomization design-and-analysis methods have been developed for the multiple-baseline, ABAB, and alternating treatment designs, including options for preplanned designs, wherein the series and phase lengths are established prior to gathering data, as well as options for response-guided designs, wherein ongoing visual analyses guide decisions about when to intervene. Our purpose here is to develop randomization methods for another class of single-case design, the changing criterion design. We first illustrate randomization design-and-analysis methods for preplanned changing criterion designs and then develop and illustrate methods for response-guided changing criterion designs. We discuss the limitations associated with the randomization methods and the validity of the corresponding intervention-effect inferences.

Case Report: A child with NFKB1 haploinsufficiency explaining the linkage between immunodeficiency and short stature.

We report the case of a patient with common variable immunodeficiency (CVID) presenting with short stature and treated with recombinant human growth hormone (rhGH). Whole exome sequencing revealed a novel single-nucleotide duplication in the NFKB1 gene (c.904dup, p.Ser302fs), leading to a frameshift and thus causing NFKB1 haploinsufficiency. The variant was considered pathogenic and was later found in the patient's mother, also affected by CVID. This is the first reported case of a patient with CVID due to NFKB1 mutation presenting with short stature. We analyzed the interconnection between NFKB1 and GH - IGF-1 pathways and we hypothesized a common ground for both CVID and short stature in our patient.

Stark coefficients for highly excited rovibrational states of H2O.

Quantum beat spectroscopy is combined with triple-resonance vibrational overtone excitation to measure the Stark coefficients (SCs) of the water molecule for 28 rovibrational levels lying from 27,600 to 41,000 cm(-1). These data provide a stringent test for assessing the accuracy of the available potential energy surfaces (PESs) and dipole moment surfaces (DMSs) of this benchmark molecule in this energy region, which is inaccessible by direct absorption. SCs, calculated using the combination of a high accuracy, spectroscopically determined PES and a recent ab initio DMS, are within the 1% accuracy of available experimental data for levels below 25,000 cm(-1), and within 4.5% for coefficients associated with levels up to 35,000 cm(-1). However, the error in the computed coefficients is over 60% for the very high rovibrational states lying just below the lowest dissociation threshold, due, it seems, to lack of a high accuracy PES in this region. The comparative analysis suggests further steps, which may bring the theoretical predictions closer to the experimental accuracy.

Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency.

Background: Zellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs). Case Presentation: We report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected. Conclusion: In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.

Congenital dacryocystocele: diagnosis and treatment.

Five children were diagnosed with congenital dacryocystocele; in all cases, the cystic lesion was unilateral; age ranged from 7 to 60 days (mean 29 days). The mean ultrasonography diameter of the cyst, at the time of the diagnosis, was 11.51 mm. Topical and systemic antibiotics and massage were prescribed. One patient had no recurrence of the dacryocystocele but 4 showed no improvement with medical treatment; they were submitted to successful probing in the first months of life under general anaesthesia. Nasal endoscopy revealed a nasolacrimal cyst in one patient. True dacryocystocele is relatively rare: ultrasound is a simple, non-invasive method that can reliably distinguish dacryocystocele from other pathological conditions. Several reports have described a variable natural course of these lesions but there are controversial opinions regarding their management. Initially, we treated this congenital anomaly with digital massage, and topical and systemic antibiotics. Probing under general anaesthesia was performed in the event of dacryocystitis or lack of resolution after a short trial period with digital massage. Particular attention was paid to nasal bilateral endoscopy to exclude a nasal obstruction caused by cystic swelling of the nasolacrimal duct. When performed, the probing procedure was successful in all patients.

[Instruments and accessories for interventional endoscopic ultrasonography]. / Strumenti e accessoriper ecoendoscopia interventistica.

Endoscopic ultrasound-guided (EUS) biopsy is now an established method for acquisition of cytohistological specimens. Some other procedures can be performed successfully in most instances (e.g., celiac plexus block, pseudocystic drainage), and some are being performed but need further refinement or validation (e.g., pancreatic and biliary drainage, ablation of pancreatic cyst neoplasm). The present review describes the interventional endoscopes, the needle systems and the specific devices for other interventional procedures available on the market.

Close relation between cirrhosis and gallstones: cross-sectional and longitudinal survey.

BACKGROUND: Increased gallstone prevalence and incidence in cirrhosis have already been reported in different series, including a limited number of patients with cirrhosis. OBJECTIVE: To evaluate the frequency of gallstones and related risk factors in a large series of patients with cirrhosis. PATIENTS AND METHODS: The cross-sectional study involved 1010 patients with cirrhosis related to alcohol abuse, chronic viral infection, or miscellaneous causes (42%, 48%, and 10%, respectively) in Child class A, B, or C (48%, 36%, and 16%, respectively). In the longitudinal study gallstone development was monitored ultrasonographically in 618 patients free of gallstones at enrollment. RESULTS: The overall prevalence of gallstone(s) was 29.5% and increased significantly with age without differences according to sex or cause of cirrhosis. Multiple logistic regression analysis showed that only Child classes B and C were significantly related to a higher risk of gallstone (odds ratio, 1.63 for class C vs class A and 1.91 for class B vs class A; P = .001). During a mean+/-SD follow-up of 50 months+/-9 months, 141 (22.8%) of 618 patients developed gallstone(s), with an estimated cumulative probability of 6.5%, 18.6%, 28.2%, and 40.9% at 2, 4, 6, and 8 years, respectively. Multivariate analysis showed that Child class (hazard ratio, 2.8 for class C vs class A and 1.8 for class B vs class A; P = .002 and P = .001, respectively) and high-body mass index (hazard ratio, 1.31; P = .04) carried a significantly greater risk of gallstone formation. CONCLUSION: Cirrhosis per se represents a major risk factor for gallstones whose prevalence and incidence were far higher than those reported in a general population from the same area.

Immune and neuroendocrine response to restraint in male and female rats.

A parallel study of the modification in the opioid and immunological systems induced by acute restraint (RT) was carried out in male and female rats 24 hr after the treatment. beta-Endorphin-like immunoreactivity (beta-ELI) was measured in two brain areas (ventral hypothalamus [HYP] and periaqueductal gray matter [PAG]) and in the pituitary (anterior and neurointermediate lobes), together with plasma corticosterone (C) and ACTH. Immune function was measured as mitogen-induced Interferon-gamma (IFN-gamma) production by splenocytes. RT reduced beta-ELI levels in the PAG in males and females. Plasma levels of C and ACTH did not differ from the basal levels in restrained animals. RT reduced IFN-gamma production in both sexes, but this effect was more marked in females than in males. The possible relationship between the immune and opioid system is discussed.

Decrease of hippocampal choline acetyltransferase activity induced by formalin pain.

The involvement of the hippocampal choline acetyltransferase (ChAT) activity in the response to tonic pain was investigated in rats injected with formalin, either 50 microliters 10% or 50 microliters 0.1%. Hippocampal ChAT activity was found to be reduced both 30 and 60 min after injection of the higher concentration of formalin but only 30 min after the lower one. Results indicate that the decrease in ChAT activity depends upon the presence of the nociceptive input rather than its magnitude. The hippocampal formation is involved in the specific behavioural response to pain, namely licking.

Testosterone metabolism in the olfactory epithelium of intact and castrated male rats.

To study the ability of the olfactory epithelium (OE) to transform testosterone (T) into its active metabolites estradiol (E2) and dihydrotestosterone (DHT), and the influence of castration on this ability, 24 adult male rats were either castrated, and subsequently treated with oil or T, or sham operated. In all groups the in vitro conversion of T by the OE into E2 and DHT is relevant, demonstrating for the first time the presence of aromatase and of 5 alpha-reductase in this tissue. In particular conversion of T into E2 is lowered by castration and restored by T replacement, suggesting that aromatization in this tissue is androgen dependent. The ability of circulating T to influence morphological and physiological features of the OE suggests the hypothesis that androgens may vary the functioning of the olfactory apparatus and modulate the efficiency by which olfactory information is conveyed to the brain.

Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to age and to sport activity.

Glucocorticoid receptors (GR) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues. Peripheral blood mononuclear cells (PBMCs) are a good model for studies of GR in humans. Glucocorticoids are important for maintaining cellular and humoral homeostasis and are key mediators of neuroendocrine-immune regulatory interactions. The increase of cortisol is immunosuppressive and reduces GR concentration both in nervous and immune systems. Variation of glucocorticoids in healthy aged subjects and athletes has been shown. Prompted by these results, we have investigated in man a possible relationship between GR binding capacity in the PBMCs and age, in relation also to plasma testosterone and cortisol. The same parameters have been examined in a group of soccer players for comparison with the sedentary group. GR binding capacity was higher in younger subjects than in older ones, and lower in the group of athletes than in the younger and older sedentary subjects. In the sedentary group a negative correlation was present between GR binding capacity and age. Plasma cortisol was higher and testosterone lower in the athletes; they were negatively correlated in athletes and positively correlated in the sedentary subjects. The results for athletes agree with their lower anabolic/catabolic balance. The mechanism of reduced GR levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis. However other possibilities, such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different cytokine production, cannot be excluded. Several neuroendocrine-immune interactions could be responsible for reduced GR levels with age and sport activity in man.

Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to explosive performance in elite handball players.

Ten handball players, members of the Italian National Team (aged 20-25 years), were studied in two sessions corresponding to different performance levels. The first session occurred one week after the end of the regular season of the Italian Handball Federation: it corresponded to the beginning of the training cycle for the European Handball Championship. The second session occurred ten weeks after the first session. During this period, training consisted of 3 weeks of active recovery and 7 weeks of increasing workload. For each session, jumping performances (maximal height in a single jump, average mechanical power for a 15-s set of consecutive jumps) were evaluated. Venous blood samples were collected in resting conditions immediately before jumping performances to assess cortisol and testosterone plasma concentrations and glucocorticoid receptors (GcR) binding capacity and affinity in peripheral blood mononuclear cells (PBMCs). All the parameters, except GcR binding affinity, increased in the second session. The trends of variation in jumping performances, steroid hormone levels and GcR binding capacity were similar. For testosterone, this agrees with the hypothesis that an adequate level of this hormone is a prerequisite for improvement in explosive performances. For cortisol, higher GcR binding capacity after 10 weeks of training (with respect to initial values) indicated an up-regulation of GcR concomitant with the increase in hormone levels and performances. These findings suggest that the adaptation to training, confirmed by the improvement in performance, is characterized by a high value of GcR binding capacity and that it is mediated, among other factors, by the hormone levels and up-regulation of the receptors.

Interaction of tonic immobility and dexamethasone in the modulation of hippocampal 5-HT activity in rabbits.

The immobility reaction (animal hypnosis) in the rabbit is related to basal levels of corticosterone and to modifications in 5-HT activity in the brain. In order to investigate the relationship between adrenocortical function, brain 5-HT activity and immobility response in rabbits, the susceptibility to the reaction and 5-HT and 5-HIAA levels in the hippocampus were studied in animals whose pituitary-adrenal function was altered by chronic DEX treatment. It was still possible to induce immobility in animals treated with DEX. The reduction in duration observed under the present testing schedule (two sessions of immobility separated by a one week interval) did not occur in the treated animals. There was a reduction in 5-HT turnover as a consequence of the immobility response and this confirms previous findings in other brain areas of the same species. In animals pretreated with DEX, so as to drastically reduce ACTH and corticosterone, not only was a reduction in 5-HT turnover prevented, but there was also an increase in 5-HT and 5-HIAA levels when immobility was induced. These results are discussed in terms of the influence of the pituitary-adrenal system in the neuroendocrine and behavioural aspects of the immobility reaction.

Central and peripheral endocrine correlates of the immobility reaction in the toad Bufo bufo.

The immobility reaction, which may be regarded as an innate fear response, has been observed in several animal species including Amphibians. Its endocrine correlates were established in the newt Triturus cristatus and in the toad Bufo bufo, in which the duration of immobility is influenced by sex and mating. The aim of the present study was to investigate the possibility of a relation between immobility reaction and central hormonal receptors. Testosterone (T) binding capacity in the brain and plasma sex steroids were studied in four groups of male and female sexually active and inactive toads in which the immobility reaction was induced by inversion (A) and by inversion +pressure (B). Females were found to be more susceptible than males to immobility A, whereas males were more susceptible to B. Sexually active animals with higher plasma levels of sex steroids were less susceptible than inactive ones. Lower T binding capacity in the brain and higher affinity is associated with sexual activity. Susceptibility to the immobility was negatively correlated with plasma sex steroids and positively correlated with T binding capacity. A reciprocal effect was found to exist between endocrine parameters at central and peripheral level, both controlling immobility behaviour. Mating may influence susceptibility to immobility through an endocrine mechanism.

Hippocampal cholineacetyltransferase activity, agonistic behaviour and social stress in male rabbits.

Agonistic behaviour was observed in pairs of unfamiliar male rabbits living in an outdoor enclosure. Attack, Chase, Follow and Cross-over were scored. On the basis of their frequencies the subjects in the pair were assigned a first or second rank-position. Hippocampal cholineacetyltransferase (ChAT) and plasma levels of corticosterone were considered in relation to rank. ChAT levels in the dorsal hippocampus varied in relation to agonistic behaviour. Second-ranking subjects had significantly higher levels of ChAT than the first-ranking animals and had levels of corticosterone which were markedly higher at the end of the experimental period than at the beginning. A negative correlation was found between Attack and ChAT levels in the dorsal hippocampus. These results suggest the presence of social stress in the second-ranking animals and indicate a state of activation of the hippocampus in relation to agonistic behaviour.

Testosterone binding sites in the brain, plasma sex hormones and reproductive behaviour in males of the toad Bufo bufo.

The central action of steroid hormones of the regulation of reproductive behaviour has been recognized in Amphibia, as in, other Vertebrates. Central and peripheral endocrine aspects of reproductive behaviour were studied in the toad Bufo bufo during the breeding aspects of reproductive behaviour were studied in the toad Bufo bufo during the breeding (DHT) and estradiol (E) levels. In the first experiment the effect of early and late entrance into the breeding pond and the difference between animals entering and leaving was established: DHT and E plasma levels, as well as T binding capacity in the brain were lower in animals leaving the pond at the end of the breeding season; animals entering early in the season showed higher levels of E than those entering late. In the second experiment the hormonal effect of amplexus and spawning was established: single males showed lower plasma DHT, higher plasma E and higher T binding values in the brain than males paired with a female. Males in amplexus with a non-spawning female showed higher plasma E levels than those with a spawning female. These results show that it is possible to relate the different reproductive success to different T binding in the brain. The effect of amplexus on potential responsiveness to steroid hormones at the central level and on peripheral hormone concentrations suggests the presence of a regulatory mechanism which is more active when both amplexus and spawning occur. On the other hand, the data concerning animals entering and leaving the pond indicate that the hormonal variations are not due solely to the end of sexual behaviour since the difference is already significant between groups entering early and late in the breeding season.

Increased uptake of radio labelled white blood cells into abdomen of uremics on peritoneal dialysis.

Peritonitis and exit-site tunnel infection are frequent causes of CAPD drop out. We studied 9 patients, 8 treated by CAPD and 1 by IPD. These patients underwent sonographic and scintigraphic study of the abdomen. All scintigraphic examinations showed a visceral uptake. In two cases, sub-clinical bowel inflammation, demonstrated by scintigraphic study, preceded a gram negative peritonitis. The scintigraphic study with radiolabelled white blood cells may be useful in identifying chronic aseptic inflammations and some bowel and exit-site conditions which are possible risk factors in some cases of peritonitis.

[Isthmic coarctation of the aorta. Description of an anomalous case]. / Coartazione istmica dell'aorta. Descrizione di un caso anomalo.

An anomalous (because of the advanced age of its onset) case of isthmic coarctation of the aorta in preductal site observed at the persistence of hypertensive symptomatology associated with cephalgic and lipothymic attacks is reported. Instrumental examinations confirmed the clinical suspicion and resective-reconstructive surgical treatment led to complete resolution of both cause and effect.

Emotional behavior in female rabbits: hippocampal EEG and neuroendocrine aspects.

Behavior, hippocampal electrical activity, plasma hormones and hippocampal choline acetyltransferase (ChAT) were considered in two groups of female rabbits, different in age and condition of breeding, both in the presence and absence of emotional stimuli. In the two groups of female rabbits (4 and 18 months old), permanent electrodes were implanted bilaterally in the two dorsal hippocampi and, one week later, the animals were exposed for three consecutive days to the following tests: Day 1, novel environment (NE); Day 2, object with odor (O); Day 3, sparrow hawk (SP). Behavior: in comparison with Day 1, exploration was decreased by the object and by the sparrow hawk in the older females and increased in the younger ones. Quiet and alert immobility was higher during the SP test, while freezing and pointing were lower in the older females than in the young ones. Electrical activity: peak frequency was lower in younger females than in the older ones. The frequency band distribution corresponding to exploration and immobility showed that in the older females the % of high frequency band increased from the first to the third day of testing, while an opposite trend was present in the younger females. In the case of freezing the hippocampal electric activity showed a more rhythmical component in younger females than in the older ones. Hormones: increased corticosterone levels after the SP test were directly correlated with exploration and inversely correlated with freezing. Dorsal hippocampal ChAT was directly correlated with quiet immobility. These data indicate a relationship between the responses to the anxious/fearful stimuli and the age and/or breeding experience of the female rabbits; this is shown by both the hippocampal electrical activity and the behavioral differences between the two groups.

[Hepatitis C and dentistry. Review of the literature]. / Epatite C ed odontoiatria. Rassegna della letteratura.

In 1988 the RNA virus responsible for the majority of cases of parenteral non A, non B hepatitis (NANBH) was isolated and designated Hepatitis C Virus (HCV). Since then, the sequence of the genome of the virus has been defined and at least 10 different types identified. Clinical studies indicate that the majority of patients who acquire HCV develop chronic hepatic disease, in particular chronic active hepatitis or cirrhosis and some of them will develop hepatocellular carcinoma. Currently, there is no effective anti-HCV therapy and no passive or active immunization protocol for HCV. Epidemiological studies indicate that HCV infection is relatively well confined to specific patient populations, in particular injecting drug users and recipients of blood and blood products. Nevertheless as HCV infection is transmitted mainly parenterally it must be regarded as a potential hazard for dental health care staff. This article reviews current knowledge concerning HCV infection with particular attention to those issues relevant to the dentists in Italy including the dental management of the HCV infected patient and the risk of HCV cross-infection in the dental environment.