Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Subcutaneous immunoglobulin for maintenance therapy in stiff-person syndrome: One-year follow-up in two patients.

Stiff person syndrome is a rare condition characterised by prolonged stiffness with superimposed muscle spasms. Immunotherapy relies mainly on intravenous immunoglobulin, steroids and plasma exchange. Azathioprine or rituximab are other possible options. We describe two patients who showed a good clinical response with intravenous immunoglobulin and persistence of the clinical improvement after shifting to equivalent dosage of subcutaneous immunoglobulin. Both patients received a diagnosis of stiff person syndrome based on their clinical symptoms (episodes of stiffness and spasms) and presence of antiglutamic acid decarboxylase. Treatment with intravenous immunoglobulin was started with improvement of symptoms as reported by patients and confirmed also by the spasm frequency scale and modified Ashworth scale. After clinical stabilisation in order to avoid the hospitalisation required for intravenous immunoglobulin treatment a switch to subcutaneous immunoglobulins was made. After one year of follow-up from the switch, the patients show clinical stability. Their scores on the modified Ashworth scale, spasm frequency scale and on the 10 Meter Walking Test were also stable. Subcutaneous formulation of immunoglobulin could be as effective as intravenous immunoglobulin in the maintenance treatment of Stiff person syndrome, although studies involving a larger cohort of patients are needed in order to confirm our anecdotal experience.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS: All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. CONCLUSIONS: Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.

Predictors of mortality in nursing-home residents with pneumonia: a multicentre study.

OBJECTIVES: To evaluate predictors of mortality in patients residing in nursing-homes (NHs) or long-term care facilities (LTCFs) with diagnosis of NH-acquired pneumonia (NHAP). METHODS: We conducted an observational, prospective study (December 2013-December 2015) of patients residing in nine NHs/LTCFs of Central and Northern Italy with diagnosis of NHAP. Data on demographics, comorbidities, microbiology, and therapies were entered into an electronic database. To identify risk factors associated with 30-day mortality, we performed univariable and multivariable analyses, and predictors were internally validated using a bootstrap resampling procedure. We derived a prediction rule using the coefficients obtained from the multivariable logistic regression. The model obtained was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Overall, 446 patients with NHAP were included in the final cohort. The median age was 80 (IQR 75-87) years. A definite aetiology was obtained in 120 (26.9%) patients; of these, 66 (55%) had a culture positive for a multidrug-resistant pathogen. The 30-day mortality was 28.7%. On multivariate analysis, malnutrition (OR 7.8; 95% CI 3-20.2, 2 points), bilateral pneumonia (OR 3.7; 95% CI 1.4-9.8, 1 point), acute mental status deterioration (OR 6.2; 95% CI 2.2-17.6, 2 points), hypotension (OR 7.7; 95% CI 2.3-24.9, 2 points), and PaO2/FiO2 ratio ≤250 (OR 7.4; 95% CI 2.2-24.2, 2 points) were independently associated with 30-day mortality. The derived prediction rule showed an AUROC of 0.83 (95% CI 0.78-0.87, p <0.001). CONCLUSIONS: NH residents with pneumonia have specific risk factors associated with 30-day mortality. Malnutrition and acute mental change appear as major determinants of death in this population.

A retrospective review of an epidural blood patch database: the incidence of epidural blood patch associated with obstetric neuraxial anesthetic techniques and the effect of blood volume on efficacy.

BACKGROUND: The optimal volume of blood required to treat post-dural puncture headache remains in question. In our institution a target volume of 30mL is used for an epidural blood patch unless the patient experiences pain during injection. METHODS: The institutional database was retrospectively reviewed for epidural blood patch and delivery statistics over a 15-year period to determine if the volume of blood administered during the procedure directly correlated with the number of epidural blood patches administered. The primary endpoint was defined as the need for a repeat epidural blood patch. RESULTS: There were 466 epidural blood patches performed on 394 patients, associated with 84 804 obstetric neuraxial procedures. Thirty-two percent (95% CI 28.3 to 34.9%) of patients who had an inadvertent dural puncture with an epidural needle received an epidural blood patch versus 0.19% (0.16% to 0.22%) of patients who received neuraxial anesthesia with no documented dural puncture with an epidural needle. All patients experienced relief of post-dural puncture headache, although 17% required two and 1.5% required three epidural blood patches. The mean±SD volume of blood administered was 20.5±5.4mL and only 35 patients (8.9%) received 30mL. CONCLUSION: Increasing blood volumes up to 30mL did not reduce the need for repeat epidural blood patch. Although the optimal volume of blood to administer during epidural blood patch placement remains unknown, our institution will continue to administer up to 30mL or until the patient experiences pain during epidural injection.

Post-ganglionic autonomic neuropathy associated with anti-glutamic acid decarboxylase antibodies.

PURPOSE: Antibodies to glutamic acid decarboxylase (GAD-Abs) have been associated with several conditions, rarely involving the autonomic nervous system. Here, we describe two patients complaining of autonomic symptoms in whom a post-ganglionic autonomic neuropathy has been demonstrated in association with significantly elevated serum and CSF GAD-Abs levels. METHODS: Patients underwent nerve conduction studies, sympathetic skin response testing, evaluation of autonomic control of the cardiovascular system and skin biopsy. Also, serum screening to exclude predisposing causes of peripheral neuropathy was performed. Anti-GAD65 antibodies were evaluated in serum and CSF. RESULTS: GAD-Abs titer was increased in both serum and CSF in both patients. Sympathetic skin response was absent and skin biopsy revealed a non-length-dependent small-fiber neuropathy with sympathetic cholinergic and adrenergic post-ganglionic damage in both patients. Nerve conduction studies and evaluation of autonomic control of the cardiovascular system were normal in both patients. Both patients were treated with steroids with good, but partial, (patient 2) recovery of the autonomic dysfunctions. CONCLUSIONS: Although the pathophysiological mechanisms involved are not fully defined, GAD-abs positivity in serum and CSF should be searched in patients with autonomic neuropathy when no other acquired causes are evident. This positivity may help to clarify autoimmune etiology and, subsequently, to consider immunomodulatory treatment.

Allergy in urban elderly population living in Campania region (Southern Italy). A multicenter study.

Given the increasing life expectancy observed in Western countries, there is a marked interest to know more about how aging could influence respiratory health. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic elders living in Campania region area (Southern Italy). Fourteen Allergy units or Centres examined a total of 462 patients. In this context 215 (46.53%) had positive skin prick tests (SPTs) to at least one allergen and were diagnosed with respiratory allergy. Parietaria represents the most common sensitizing agent in elders living in Campania region, followed by dust mites, grass pollen and Olea europaea. A relatively high percentage of atopic subjects suffered from respiratory symptoms at a fairly advanced age, namely 8.3% at 60-64 years, 10.2% at 65-70 and 5.7% at > 70 years. In conclusion, the prevalence and clinical significance of airway allergic sensitization in the elderly living in Campania region is more significant than expected in latter stages of life. Physicians should not neglect the role of atopy as a risk factor for the onset of allergic respiratory symptoms even in elderly patients.

Three dimensional graphene scaffold for cardiac tissue engineering and in-situ electrical recording.

In this paper, we present a three-dimensional graphene foam made of few layers of CVD grown graphene as a scaffold for growing cardiac cells and recording their electrical activity. Our results show that graphene foam not only provides an excellent extra-cellular matrix (ECM) for the culture of such electrogenic cells but also enables recording of its extracellular electrical activity in-situ. Recording is possible due to graphene's excellent conductivity. In this paper, we present our results on the fabrication of the graphene scaffold and initial studies on the culture of cardiac cell lines such as HL-1 and recording of their real-time electrical activity.

GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

Occupational Exposure to Chromium of Assembly Workers in Aviation Industries.

Aircraft are constructed by modules that are covered by a "primer" layer, which can often contain hexavalent chromium [Cr(VI)], known carcinogen to humans. While the occupational exposure to Cr(VI) during aircraft painting is ascertained, the exposure assessment of assembly workers (assemblers) requires investigations. Three biological monitoring campaigns (BM-I,II,III) were performed in an aviation industry, on homogeneous groups of assemblers (N = 43) and controls (N = 23), by measuring chromium concentrations in end-shift urine collected at the end of the working week and the chromium concentration difference between end- and before-shift urines. BM-I was conducted on full-time workers, BM-II was performed on workers after a 3-4 day absence from work, BM-III on workers using ecoprimers with lower Cr(VI) content. Samples were analyzed by atomic absorption spectroscopy and mean values were compared by T-test. Even if Cr concentrations measured during BM-I were lower than Biological Exposure Indices by ACGIH, statistically significant differences were found between urinary Cr concentrations of workers and controls. Despite 3-4 days of absence from work, urinary chromium concentrations measured during BM-II were still higher than references from nonoccupationally exposed populations. In the BM-III campaign, the obtained preliminary results suggested the efficacy of using ecoprimers. The healthcare of workers exposed to carcinogenic agents follows the principle of limiting the exposure to "the minimum technically possible". The obtained results evidence that assemblers of aviation industries, whose task does not involve the direct use of primers containing Cr(VI), show an albeit slight occupational exposure to Cr(VI), that must be carefully taken into consideration in planning suitable prevention measures during risk assessment and management processes.

SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model.

Somatic mutations or deletions of TP53 and PTEN in ductal carcinoma in situ lesions have been implicated in progression to invasive ductal carcinomas. A recent molecular and mutational analysis of breast cancers revealed that inactivation of tumor suppressors, p53 and PTEN, are strongly associated with triple negative breast cancer. In addition, these tumor suppressors have important roles in regulating self-renewal in normal and malignant stem cells. To investigate their role in breast carcinogenesis, we knocked down these genes in human mammary cells and in non-transformed MCF10A cells. p53 and PTEN knockdown synergized to activate pro-inflammatory interleukin-6 (IL6)/Stat3/nuclear factor κB signaling. This resulted in generation of highly metastatic epithelial-to-mesenchymal transition-like cancer stem cells resulting in tumors whose gene expression profile mimicked that found in basal/claudin-low molecular subtype within the triple negative breast tumors. Constitutive activation of this loop in transformed cells was dependent on proteolytic degradation of suppressor of cytokine signaling 3 (SOCS3) resulting in low levels of this protein in basal/claudin-low cell lines and primary tumors. In non-transformed cells, transient activation of the IL6 inflammatory loop induced SOCS3 expression leading to pathway inactivation. In transformed cells, enforced expression of SOCS3 or interfering with IL6 pathway via IL6R blockade inhibited tumor growth and metastasis in mouse xenograft models. Furthermore, circulating tumor cells were significantly reduced in tumor-bearing animals when treated with anti-IL6R antibodies. These studies uncover important connections between inflammation and carcinogenesis and suggest that blocking pro-inflammatory cytokines may be utilized as an attractive strategy to target triple negative breast tumors, which currently lacks molecularly targeted therapies.

Anesthetic and obstetric outcomes in morbidly obese parturients: a 20-year follow-up retrospective cohort study.

BACKGROUND: In 1993, Hood and Dewan published the results of a trial comparing obstetric and anesthetic outcomes of 117 morbidly obese parturients with matched controls. The authors demonstrated a higher initial epidural anesthesia failure rate, a higher cesarean delivery rate and an increased risk of obstetric complications. We replicated the previous study to provide updated information on outcomes in the morbidly obese pregnant population. We hypothesized that morbidly obese women would still have higher complication and failure rates compared to matched controls and that general anesthesia would be less commonly used than in the previous study. METHODS: The medical records of 230 patients weighing >136 kg (300 pounds) were compared to matched controls: the next patient delivered by the same obstetrician with a weight <113 kg (250 pounds). RESULTS: The mean body mass index of the morbidly obese group was 53.4 ± 6.6 kg/m² [corrected] compared to 31.1±5.4 kg/m2 in the control group. Fifty percent of morbidly obese women required cesarean delivery compared to 32% of controls (P < 0.01). Morbidly obese patients had a longer first stage of labor (P < 0.01), larger neonates (P < 0.01), and were more likely to have a failed initial neuraxial technique for labor analgesia (P < 0.01). The need for a replacement procedure for labor was 17%, significantly less than 20 years ago when 42% of catheters in morbidly obese women failed (P < 0.01). Failure rates of neuraxial anesthesia for cesarean delivery were similar between groups. Neuraxial procedure times were greater in morbidly obese parturients (P < 0.01). Morbidly obese women were less likely to receive general anesthesia compared to 20 years ago (3% vs. 24%, P < 0.01). CONCLUSIONS: Morbidly obese parturients are still at increased risk for antenatal comorbidities, failed labor analgesia, longer first stage of labor and operative delivery. Replacement labor epidural catheters and general anesthesia for cesarean delivery are less commonly required anesthetic techniques compared to the original study.

Neuropathic pain following spinal cord injury: what we know about mechanisms, assessment and management.

BACKGROUND: In biology, it is easy to understand how a damaged functional system may generate wrong signals, but why this should happen when the system is disconnected is less clear. For this reason, among other pain syndromes, neuropathic pain (NP) following spinal cord injury (SCI) leaves most questions unanswered. AIMS AND METHODS: Our purpose is to review current knowledge on NP after SCI, focusing on the mechanisms, assessment and management of the syndrome. RESULTS: The mechanisms responsible for NP following SCI are poorly understood: NP is classically considered a "central pain syndrome" but recent evidence from experimental models reveals a possible "peripheral sensitization". Assessment of NP following SCI is well-established: in addition to clinical evaluation and self-reported scales, many neurophysiological, radiological and microscopic investigations may be performed. The management of NP following SCI is very difficult: evidence of effective drugs is lacking and alternative new treatment approaches yield different outcomes. CONCLUSIONS: Recently clinical and instrumental tools have increased our knowledge on NP, suggesting that the discovery of new treatment agents will depend on an explanation of what changes after SCI: future research must point in this direction.

[Asbestos: fifty years of work exposure in Campania and other Italian regions through INAIL experience]. / Amianto: un cinquantennio di esposizione lavorativa in Campania e nelle altre regioni d'Italia attraverso le competenze INAIL.

The aim of the work is to proceed to the recognition of asbestos phenomenon in Campania and in the other regions with emphasis on the incidence and development of several related diseases. Using data from first INAIL Annual Report on the progress of occupational diseases until 1999, and the data provided by the INAIL CSA regarding the last 12 years (2000 to 2011), the incidence is illustrated for two-year periods, from 2000 to 2011, for the total of diseases and separately for: asbestosis, mesotheliomas, lung cancer and non-cancerous pleural lesions. The total of diseases by region for the period 2000-2011 has been reported. The survey results show a gradual increase in the total asbestos related diseases (15,998) due to the mesotheliomas portion (5739) while the trend of lung cancer is stationary (2,287). Pleural plaques have a variable growth in the various regions during recent years. Some significant case studies from Campania are reported.

Healthcare-acquired infections in rehabilitation units of the Lombardy Region, Italy.

BACKGROUND: Little data are available on the frequency and risk factors for infection in patients in rehabilitation units. METHODS: This was a 2-year retrospective cohort study conducted in 131 rehabilitation units (RUs) of the Lombardy Region, including those for patients requiring musculoskeletal, cardiac, respiratory, neurological and general geriatric rehabilitation. RUs were stratified into three groups by infection rate calculated from administrative data, and a random sample of RUs in each group was selected for analysis. Discharges from these RUs were randomly selected for chart review, and healthcare-acquired infection was confirmed using CDC/NHSN definitions. A logistic regression analysis explored the association among demographic variables of age, sex, type of rehabilitation unit, Charlson comorbidity score, and location prior to RU admission for selected infections. RESULTS: For the 3,028 discharges from 28 RUs, hospital administrative data had a sensitivity of 0.45 and a positive predictive value of 0.89 to identify infections in the chart review. At least one infection occurred in 14.9% of patient discharges, with 71% of infections being urinary, 8.0% respiratory, and 5% skin and soft tissue. Urinary infection was associated with female sex [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.13-1.93], age 75-85 years (OR 2.21, 95% CI 1.12-4.34), Charlson comorbidity score of ≥3 (OR 1.54, 95% CI 1.10-2.17), and the transfer from acute care (OR 1.45, 95% CI 1.04-2.02). For respiratory infection, male sex (OR 3.06, 95% CI 1.51-6.18), comorbidity score of 1 or 2 (OR 2.16, 95% CI 1.08-4.36), and transfer from a healthcare setting other than an acute care hospital were independent risks (OR 3.14, 95% CI 1.15-8.53). CONCLUSION: Infections are common in residents of these rehabilitation units, and risk factors may differ with type of infection. The proportion of infections which may be prevented and effective prevention strategies need to be determined.

Native human adipose stromal cells: localization, morphology and phenotype.

OBJECTIVES: Beside having roles in energy homeostasis and endocrine modulation, adipose tissue (AT) is now considered a promising source of mesenchymal stromal cells (adipose-derived stromal cells or ASCs) for regenerative medicine. Despite numerous studies on cultured ASCs, native human ASCs are rarely investigated. Indeed, the phenotype of ASCs in their native state, their localization within AT and comparison with bone marrow-derived mesenchymal stromal cells (BM-MSCs) has been poorly investigated. DESIGN: To address these issues, the stroma vascular fraction (SVF) of human AT was extracted and native cell subtypes were isolated by immunoselection to study their clonogenic potential in culture. Immunohistology on samples of human AT in combination with reconstruction of confocal sections were performed in order to localize ASCs. RESULTS: Compared with BM-MNCs, all native ASCs were found in the CD34(+) cell fraction of the AT-SVF. Native ASCs expressed classical mesenchymal markers described for BM-MSCs. Interestingly, CD34 expression decreased during ASC cell culture and was negatively correlated with cell proliferation rate. Immunohistological analysis revealed that native ASCs exhibited specific morphological features with protrusions. They were found scattered in AT stroma and did not express in vivo pericytic markers such as NG2, CD140b or alpha-smooth muscle actin, which appeared during the culture process. Finally, ASCs spontaneous commitment to adipocytic lineage was enhanced in AT from obese humans. CONCLUSIONS: The use of complementary methodological approaches to study native human ASCs revealed their immunophenotype, their specific morphology, their location within AT and their stemness. Furthermore, our data strongly suggest that human ASCs participate in adipogenesis during AT development.

Three wave mixing test of hyperelasticity in highly nonlinear solids: sedimentary rocks.

Measurements of three-wave mixing amplitudes on solids whose third order elastic constants have also been measured by means of the elasto-acoustic effect are reported. Because attenuation and diffraction are important aspects of the measurement technique results are analyzed using a frequency domain version of the KZK equation, modified to accommodate an arbitrary frequency dependence to the attenuation. It is found that the value of beta so deduced for poly(methylmethacrylate) (PMMA) agrees quite well with that predicted from the stress-dependent sound speed measurements, establishing that PMMA may be considered a hyperelastic solid, in this context. The beta values of sedimentary rocks, though they are typically two orders of magnitude larger than, e.g., PMMA's, are still a factor of 3-10 less than those predicted from the elasto-acoustic effect. Moreover, these samples exhibit significant heterogeneity on a centimeter scale, which heterogeneity is not apparent from a measurement of the position dependent sound speed.

Catathrenia (nocturnal groaning): an abnormal respiratory pattern during sleep.

Catathrenia (nocturnal groaning) is a rare condition characterized by monotonous irregular groans occurring during sleep. Ten patients (five women; mean age: 27 +/- 7.4 years, range: 15-41) with sleep-related groaning persisting for years or decades and normal daytime fibreoptic laryngoscopy and respiratory function tests underwent videopolysomnographic recording (VPSG) analysing their respiratory patterns during sleep. After the VPSG, all patients were clinically followed up for a mean period of 4.9 +/- 3.5 years. On VPSG, all patients showed nocturnal groaning during NREM sleep and particularly during REM sleep stages. Groaning was associated with disproportionate prolonged expiration causing reduced breathing rate without oxygen desaturation. The breathing pattern with prolonged expiration and sound production alternated with a normal respiratory pattern without groaning. Endoesophageal pressure during groaning showed mildly positive swings at the initial phase of expiration suggesting a partial mild expiratory upper airway obstruction. At the end of the follow-up period, all patients reported persistent nocturnal groaning but no other clinical manifestations. Groaning confined to sleep alternating with normal breathing and the absence of long-term clinical consequences suggest that catathrenia is because of an abnormality of the internal respiratory drive system, possibly related to persistence of a neonatal (vestigial) type of breathing pattern.