Variation in the strength of allometry drives rates of evolution in primate brain shape.

Large brains are a defining feature of primates, as is a clear allometric trend between body mass and brain size. However, important questions on the macroevolution of brain shape in primates remain unanswered. Here we address two: (i), does the relationship between the brain size and its shape follow allometric trends and (ii), is this relationship consistent over evolutionary time? We employ three-dimensional geometric morphometrics and phylogenetic comparative methods to answer these questions, based on a large sample representing 151 species and most primate families. We found two distinct trends regarding the relationship between brain shape and brain size. Hominoidea and Cercopithecinae showed significant evolutionary allometry, whereas no allometric trends were discernible for Strepsirrhini, Colobinae or Platyrrhini. Furthermore, we found that in the taxa characterized by significant allometry, brain shape evolution accelerated, whereas for taxa in which such allometry was absent, the evolution of brain shape decelerated. We conclude that although primates in general are typically described as large-brained, strong allometric effects on brain shape are largely confined to the order's representatives that display more complex behavioural repertoires.

Simultaneous detection of macroevolutionary patterns in phenotypic means and rate of change with and within phylogenetic trees including extinct species.

Recognizing evolutionary trends in phenotypic means and rates requires the application of phylogenetic comparative methods (PCMs). Most PCMs are unsuited to make full use of fossil information, which is a drawback, given the inclusion of such data improves, and in some cases even corrects, the proper understanding of trait evolution. Here we present a new computer application, written in R, that allows the simultaneous computation of temporal trends in phenotypic mean and evolutionary rate along a phylogeny, and to contrast such patterns among different clades within the tree. By using simulation experiments, we show the new implementation, names search.trend is as powerful as existing PCM tools in discerning macroevolutionary patterns in phenotypic means and rates, but differently from any other PCM allows comparing individual clades to each other, and provides rich information about trait evolution for all lineages in the tree.

Unexpectedly rapid evolution of mandibular shape in hominins.

Members of the hominins - namely the so-called 'australopiths' and the species of the genus Homo - are known to possess short and deep mandibles and relatively small incisors and canines. It is commonly assumed that this suite of traits evolved in early members of the clade in response to changing environmental conditions and increased consumption of though food items. With the emergence of Homo, the functional meaning of mandible shape variation is thought to have been weakened by technological advancements and (later) by the control over fire. In contrast to this expectation, we found that mandible shape evolution in hominins is exceptionally rapid as compared to any other primate clade, and that the direction and rate of shape change (from the ape ancestor) are no different between the australopiths and Homo. We deem several factors including the loss of honing complex, canine reduction, and the acquisition of different diets may have concurred in producing such surprisingly high evolutionary rates. This study reveals the evolution of mandibular shape in hominins has strong morpho-functional and ecological significance attached.

Progress to extinction: increased specialisation causes the demise of animal clades.

Animal clades tend to follow a predictable path of waxing and waning during their existence, regardless of their total species richness or geographic coverage. Clades begin small and undifferentiated, then expand to a peak in diversity and range, only to shift into a rarely broken decline towards extinction. While this trajectory is now well documented and broadly recognised, the reasons underlying it remain obscure. In particular, it is unknown why clade extinction is universal and occurs with such surprising regularity. Current explanations for paleontological extinctions call on the growing costs of biological interactions, geological accidents, evolutionary traps, and mass extinctions. While these are effective causes of extinction, they mainly apply to species, not clades. Although mass extinctions is the undeniable cause for the demise of a sizeable number of major taxa, we show here that clades escaping them go extinct because of the widespread tendency of evolution to produce increasingly specialised, sympatric, and geographically restricted species over time.

Survey of tuberculosis drug resistance among Tibetan refugees in India.

SETTING: Tuberculosis (TB) is a major health problem among Tibetans living in exile in India. Although drug-resistant TB is considered common in clinical practice, precise data are lacking. OBJECTIVE: To determine the proportion of drug-resistant cases among new and previously treated Tibetan TB patients. DESIGN: In a drug resistance survey in five Tibetan settlements in India, culture and drug susceptibility testing (DST) for first-line drugs were performed among all consecutive new and previously treated TB cases from April 2010 to September 2011. DST against kanamycin (KM), ethionamide, para-aminosalicylic acid and ofloxacin (OFX) was performed on multidrug-resistant TB (MDR-TB) isolates. RESULTS: Of 307 patients enrolled in the study, 264 (193 new and 71 previously treated) were culture-positive and had DST available. All patients tested for the human immunodeficiency virus (n = 250) were negative. Among new TB cases, 14.5% had MDR-TB and 5.7% were isoniazid (INH) monoresistant. Among previously treated cases, 31.4% had MDR-TB and 12.7% were INH-monoresistant. Of the MDR-TB isolates, 28.6% of new and 26.1% of previously treated cases were OFX-resistant, while 7.1% of new cases and 8.7% of previously treated cases were KM-resistant. Three patients had extensively drug-resistant TB. CONCLUSIONS: MDR-TB is common in new and previously treated Tibetans in India, who also show additional complex resistance patterns. Of particular concern is the high percentage of MDR-TB strains resistant to OFX, KM or both.

Positive compared with negative margins in a single-centre retrospective study on 3957 consecutive excisions of basal cell carcinomas. Associated risk factors and preferred surgical management.

The rate of margins involvement and the associated recurrence risk in basal cell carcinomas (BCCs) varies widely in published works (7%-25% and 26%-67%, respectively). This study investigated the risk factors associated with incomplete excision and their relevance in surgical management when positive margins occur in 3957 BCCs excised in 2358 patients. This study performed a multivariate analysis on the database collected from all patients operated for BCCs in the Plastic Surgery Department between 1 January 1992 and 1 September 2007. All data collected (3957 excisions; 2358 individuals) were divided into complete and incomplete excisions groups and analyzed according to 14 variables. The overall rate of incomplete excisions was 14%. Mean age (68), size of the lesion (< 0.5 cm), BCC subtype (nodular with sclerosant aspects, sclerosant and basosquamous), location (face), infiltration depth (hypodermis and deep tissues), recurrent BCC and re-excised BCC were significantly associated with a higher rate of incomplete excision. The recurrence rate for incompletely excised tumours was 26.8%, while only 5.9% for completely excised tumours. Most of the risk factors associated to incomplete excision can be identified before surgery (by simple anamnesis and clinical examination) and successfully overcome by appropriate surgical margins. The high recurrence rate after incomplete excision and the low patient compliance towards follow-up should lead the surgeon to early re-excise residual cancer.

Adiponectin in outpatients with coronary artery disease: independent predictors and relationship with heart failure.

BACKGROUND AND AIMS: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors. METHODS AND RESULTS: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml⁻¹) to group 2 (9.1 ± 6.7 ng ml⁻¹) and group 3 (13.7 ± 7.6 ng ml⁻¹), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015). CONCLUSION: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.

Endometrial metastasis of a primitive neuroendocrine ovarian carcinoma: management and treatment of a case.

BACKGROUND: Neuroendocrine tumours are a heterogeneous group of separate clinico-pathological entities which have a common characteristic, i.e., expression of potential endocrine differentiation. In the ovary, the term "neuroendocrine" relates mainly to widely known carcinoids, but it may also be applied to rare neuroendocrine carcinomas as non-small cell type and small cell carcinomas of pulmonary type. In the literature only 11 cases of primary ovarian non-small cell neurendocrine carcinomas have been described and ten of these were associated with a surface epithelial ovarian tumour. Small cell neuroendocrine carcinoma of the ovary is a rare malignant tumour of the ovary. Advanced small cell carcinoma of the ovary is a very aggressive tumour with an overall poor prognosis and unfavourable outcome. CASE REPORT: The case reported is unique in the literature because the authors describe a rare case of endometrial metastasis of a primary ovarian non-small cell neurendocrine carcinoma without any surface epithelial ovarian tumour association. The tumour invaded up to less than half of the myometrium. The first symptoms were related to endometrial metastasis as metrorrhagia and pelvic pain while the asymptomatic presence of primary ovarian carcinoma was not acknowledged with physical examination, routine biochemistry, tumour markers, blood count and traditional transvaginal greyscale ultrasound. CONCLUSION: Magnetic resonance and three-dimensional (3D) ultrasonography with power Doppler are a great help in the diagnosis of ovarian localisation but only immunohistochemistry on histological material can provide a correct diagnosis. Immunohistochemistry expression of Ki67 is a useful marker of malignancy. Due to the rarity of this neoplasm, a general consensus for optimal treatment has yet to emerge. The reported biological aggressiveness of these tumours prompts combined treatment with radical surgery and adjuvant polychemotherapy.

Analysis of protease-activated receptor-1 and -2 in human scar formation.

Protease-activated receptor (PAR)-1 and PAR-2 are reported to contribute to the fibrotic process in a number of organs, including lung, liver, pancreas, and kidney. The aim of this study was to localize expression and biological activity of PAR-1 and PAR-2 in normal and pathological cutaneous scars. First, we investigated the immunohistochemical expression of PAR-1 and PAR-2 proteins in a series of human normal scars (NS, n = 10), hypertrophic scars (HS, n = 10), and keloids (K, n = 10). Expression of PAR-1 and PAR-2 was observed in all types of scar. Specifically, in HS and K, diffuse PAR-1 and PAR-2 positivity was found in dermal cellular areas composed of myofibroblasts, while no or minor staining was observed in the scattered fibroblasts embedded in abundant extracellular matrix in the context of the more collagenous nodules, irrespective of the type of scar. The hyperplastic epidermis overlying K was also found to be strongly PAR-1 and PAR-2 positive, whilst in most NS and HS the epidermis was faintly to moderately stained. Second, ribonuclease protection assay on paraffin-embedded specimens showed overexpression of PAR-1 and PAR-2 mRNA in K compared to NS and HS. Third, cultured human fibroblasts exposed to TGF-beta1 expressed a myofibroblast phenotype associated with overexpression of PAR-2, while PAR-1 expression was unaffected. Intracellular Ca(2+) mobilization by PAR-2 agonists in myofibroblasts was increased as compared to fibroblasts, whereas the effect of PAR-1 agonists was unchanged. Our in vivo study indicates that PAR-1 and PAR-2 are expressed in cells involved in physiological and pathological scar formation and suggests that in vitro overexpression and exaggerated functional response of PAR-2 may play a role in the function of myofibroblasts in scar evolution from a physiological repair process to a pathological tissue response.

A new approach to vulvar squamous cell carcinoma: two-year follow-up of a case report.

BACKGROUND: Vulvar carcinoma is relatively rare gynaecologic malignancy. The most prevalent vulvar cancer is squamous cell carcinoma. It is not uncommon for patients to delay seeking medical attention or for physicians to delay diagnosing the condition. This delay results in many cases being diagnosed in advanced stage. The sentinel lymph node "concept" is attractive in vulvar cancer because it has the potential to avoid a radical vulvectomy associated with uni- or bilateral inguinofemoral lymphadenectomy and, thus, to avoid the morbidity associated with formal groin dissection. CASE REPORT: A case of an 88-year-old woman with advanced local vulvar cancer is presented. A study of the inguinal-femoral lymph nodes was also conducted with intraoperative vital blue dye peritumoral injection and as the sentinel node was found to be negative for malignant metastasis, a radical vulvectomy without bilateral inguinofemoral lymphadenectomy and without additional treatment (chemotherapy and/or radiotherapy) was performed. Follow-up was performed at one, three, six, nine, 12, 18 and 24 months. No local recurrence or distant metastasis was found. CONCLUSION: The sentinel lymph node procedure allows a less aggressive treatment to be carried out in patients with invasive vulvar cancer thus reducing the complications and morbidity of treatment. Moreover, reducing the operative stress can change the overall survival and reduce the mortality linked to complications and postoperative stress.

Unusual case of cervical pregnancy after curettage for a presumptive diagnosis of intrauterine blighted ovum.

A case of cervical pregnancy after curettage for presumptive intrauterine blighted ovum is presented. The woman was successfully treated by vacuum evacuation and curettage. A 29-year-old woman, gravida 2, nulliparous, was admitted to our department at ten weeks and two days of gestation after a diagnosis of cervical pregnancy. She had been treated by curettage five days before for an initial diagnosis of intrauterine blighted ovum. Ultrasound scan examination revealed a gestational sac without foetus in the cervix four days after the first curettage. Vacuum evacuation and curettage of the cervical canal were performed and a Foley catheter was also inserted and left in place for three days. The patient was discharged in good condition on the fourth postoperative day.

[Atelectasis following cesarean section. Personal experience]. / Atelettasia secondari a taglio cesareo. Nostra esperienza.

Purpose of this paper is to evaluate the risk of ateletasis in patients that underwent surgery of the abdomen (cesarean section), since the reflex of cough in these patients is notably altered for the limitation of the diaphragmatic excursions, due to analgesic contracture. The inhibition of cough's reflex causes retention of secretions with consequent bronchial obstruction and atelectasis. Personal experience in 6 cases of atelectasis following cesarean section is reported.

Renal adaptive mechanisms in aged and hypertensive humans: possible effects of treatment.

BACKGROUND: In the aging kidney renal blood flow and glomerular filtration rate are reduced due to glomerulosclerosis. On this regard, hypertension has synergistic effects and may lead to end-stage renal disease in a significant proportion of cases. MATERIAL AND METHODS: To study the effects of antihypertensive drugs in an acute setting, we expressly designed an acute experiment to assess the renal response to mental stress (MS). In healthy elderly, the response was characterized by a prolonged and pronounced renal vasoconstriction, due to a reduction in renal autacoid modulatory capacity, particularly of prostaglandins. In older patients with isolated systolic hypertension, the response to MS was impaired, being characterized by a passive vasodilation with hyperfiltration. The effects of antihypertensive drugs were evaluated twice in adults patients with mild to moderate essential hypertension: after two weeks of pharmacological wash-out and after two weeks of treatment with the ACE-inhibitor trandolapril (4 mg), or the non-dihydropyridinic Ca2+ channel blocker verapamil (240 mg), or both (2 mg + 180 mg). RESULTS: While the three antihypertensive regimens reduced blood pressure to a similar extent, their effects on the renal response to MS were different. Each regimen re-established a renal vasoconstrictive response to adrenergic activation. However, with trandolapril, renal vasoconstriction was limited, as it occurs physiologically, to the period of blood pressure rise, while verapamil, or the combination of the two drugs, were associated with more prolonged vasoconstriction. CONCLUSIONS: Further studies are needed to confirm the nephroprotective effects of these drugs, particularly of ACE-inhibitors. These data may be a pathophysiological basis for future clinical trials.

Soluble Jagged 1 represses the function of its transmembrane form to induce the formation of the Src-dependent chord-like phenotype.

We have previously demonstrated that the expression of the soluble extracellular domain of the transmembrane ligand for Notch receptors, Jagged 1 (sJ1), in NIH 3T3 cells results in the formation of a matrix-dependent chord-like phenotype, the loss of contact inhibition of growth, and an inhibition of pro-alpha 1(I) collagen expression. In an effort to define the mechanism by which sJ1 induces this phenotype, we report that sJ1 transfectants display biochemical and cytoskeletal alterations consistent with the activation of Src. Indeed, cotransfection of sJ1 transfectants with a dominant-negative mutant of Src resulted in the loss of matrix-dependent chord formation and correlated with the restoration of type I collagen expression and contact inhibition of growth. We also report that the sJ1-mediated induction of Src activity and related phenotypes, including chord formation, may result from the inhibition of endogenous Jagged 1-mediated Notch signaling since it was not possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. Interestingly, NIH 3T3 cells transfected with dominant-negative (but not constitutively active) mutants of either Notch 1 or Notch 2 displayed a similar Src-related phenotype as the sJ1 transfectants. These data suggest that the ability of sJ1 to mediate chord formation is Src-dependent and requires the repression of endogenous Jagged 1-mediated Notch signaling, which is tolerant to the destabilization of the actin cytoskeleton, a mediator of cell migration.

Changes in renal autacoids and hemodynamics associated with aging and isolated systolic hypertension.

The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.

Cloud Detection Over Sea Surface by use of Autocorrelation Functions of Upwelling Infrared Spectra in the 800-900-cm(-1) Window Region.

A new algorithm for cloud detection over sea surface has been developed that makes use of autocorrelation and cross correlation between a real spectrum and either a synthetic or a laboratory spectrum. The scheme is intended for high-spectral-resolution satelliteborne infrared sensors that will measure the Earth's entire emission spectrum rather than the upwelling radiance in a few channels. A new index is defined with which one can determine quantitatively the degree of homogeneity of two spectra in the 800-900-cm(-1) (11.11-12.5 mum) window region. The index makes use of only the observed spectrum along with a reference synthetic spectrum and, therefore, may form the basis for an operational stand-alone cloud-detection algorithm for next-generation high-spectral-resolution infrared sensors. Application both to synthetic spectra obtained in simulation and to sea-surface real spectra recorded through the interferometric monitor for greenhouse gases is considered.

Changes in renal autacoids in aged human hypertensives.

The aging process determines several modifications of the kidney, that, however, do not provoke any dysfunction in normal conditions. But in the elderly--in the presence of stressful situations and particularly when adrenergic activation is present--the kidney is more vulnerable than in the young, and renal failure may arise. Variations typical of the aging kidney are accelerated when hypertension overlaps the physiological renal process, because both senescence and hypertension weight on the same structures, i.e. glomeruli. We studied renal hemodynamic adaptation capacity both in the healthy elderly and in patients affected by isolated systolic hypertension, in an acute experiment which requires the application of a mental stress-induced adrenergic activation. In hypertensive patients we have already demonstrated a total lack of renal adaptation capacity. In fact, while the elderly normotensives react with a prolonged and pronounced vasoconstriction, in those with isolated systolic hypertension, adrenergic activation induces a passive renal vasodilation and glomerular hyperfiltration. The anomalous adaptation capacity of renal hemodynamics is probably due to an impairment in the paracrine response of renal vasculature. Indeed in the hypertensive elderly, unlike in the normotensive one, no variations of autacoid production occur during the adrenergic activation. Following on from this, pattients affected by isolated systolic hypertension passively suffer the many hypertensive peaks which characterize their every day life. The altered renal autoregulation of the elderly with isolated systolic hypertension may explain the accelerated glomerulosclerosis and the greater incidence of renal damage and end-stage renal disease which characterize this condition. These aspects underline the primary role of the antihypertensive treatment of isolated systolic hypertension, not only for the prevention of cardiovascular mortality but also of renal damage and/or end-stage renal disease.

Successful outcome of pregnancy in a thyroidectomized-parathyroidectomized young woman affected by severe hypothyroidism.

Severe hypothyroidism was discovered in a young woman in her 29th week of pregnancy. Previously, at the age of 12 years, she had undergone thyroid surgery for Graves' disease that resulted in persistent hypothyroidism and hypoparathyroidism. After surgical excision, the patient started levothyroxine replacement therapy and had regular control of thyroid function with normal findings throughout the years. The dose of levothyroxine had not been adjusted when the pregnancy started, and at the 29th week of gestation the patient had a thyrotropin (TSH) of 72.4 microU/mL. Ultrasound studies were performed in order to monitor fetal development. The fetal parameters analyzed before the adjustment of levothyroxine therapy showed growth retardation of various degrees. All analyzed fetal parameters (biparietal diameter, cranial and abdominal circumference, humerus and femur length) improved during the last 6 weeks of gestation, showing a good correlation with the newly achieved euthyroid state of the mother. The infant was clinically euthyroid at birth and was found normal at all evaluations of the neonatal hypothyroidism screening program (1, 5, 30 days).

Impaired renal adaptation to stress in the elderly with isolated systolic hypertension.

The aim of this study was to evaluate the renal response in the elderly with isolated systolic hypertension (ISH) when an adrenergic activation, as induced by mental stress, is applied. Renal hemodynamics and kidney neurohumoral response to mental stress were studied in 8 elderly patients with ISH (aged 63 to 82 years) along with 8 elderly normotensive subjects. The study encompassed four 30-minute experimental periods (baseline, mental stress, and recovery I and II). In these patients, the mental stress-induced blood pressure rise was associated with a significant increase in both effective renal plasma flow ((131)I-labeled hippurate clearance) and glomerular filtration rate ((125)I-labeled iothalamate clearance) (+42% and +29%, respectively; P<0.01 for both), without variations in filtration fraction, while elderly normotensives reacted to adrenergic stimulation with renal vasoconstriction but with the glomerular filtration rate constant. Variations in renal vasoactive substances, which paralleled hemodynamics of the kidney, differed in the 2 groups. In normotensives, excretion (radioimmunoassay) of endothelin-1, prostaglandin E(2), and cGMP increased during the stimulus (+50%, +54%, and +59%, respectively; P<0.05). In ISH patients the release of these autacoids did not vary in any of the experimental periods. In conclusion, in patients with ISH the renal adaptive capacity to sympathetic activation is impaired, and the data may suggest that the glomerulus passively suffers the blood pressure increase, probably because of the insufficiency of the neurohumoral response, particularly in regard to the increase of endothelin-1. This hemodynamic pattern may predispose ISH patients to a higher risk of renal injury.