Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe.

European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non-steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes.

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

The Success and Evolution of a Urological "Boot Camp" for Newly Appointed UK Urology Registrars: Incorporating Simulation, Nontechnical Skills and Assessment.

BACKGROUND: Urological training has dramatically changed in recent years. Training durations are shorter and a drive toward consultant led care has reduced trainees experience. Within the UK, approximately 50 registrars annually embark on a 5-year Urology training programme, with variable levels of basic urological experience. OBJECTIVE: To describe a simulation programme aimed at delivering the knowledge and skills necessary to safely and effectively start working as a registrar in Urology by intensive training with a 1:1 faculty to delegate ratio. DESIGN, SETTING, AND PARTICIPANTS: Our course content mirrors the UK training syllabus for junior Urology registrars. We delivered 8 modules over a 4-day programme with a fifth day of assessments. Delegates level of urological knowledge, operative competency and confidence pre-, immediately post-training and at 3-months postcourse were assessed. Objective delegate and faculty feedback was also collected. Technical skills modules include; inguinoscrotal surgery, ureteroscopy, transurethral resection, urodynamics, and Botox administration as well as basic reconstructive and laparoscopic operative skills. "Nontechnical" skills included simulated ward round, out-patient, and emergency scenarios. RESULTS: Feedback from delegates and faculty members has been overwhelmingly positive. We have used this feedback to tailor the content of the course for following years. An increased knowledge level (based on mean examination scores [precourse 55.5%, postcourse 70.1%]) and operative competency was observed in all skills assessed (transurethral resection of the prostate, transurethral resection of bladder tumor, Ureteroscopy, laparoscopic skills, and instrument assembly). Operative confidence was increased immediately and at 3-months postcourse. CONCLUSIONS: Our "boot camp" course provides a realistic introduction and foundation to begin Urological practice. Being delivered at the beginning of the training scheme, prior to intensive patient exposure, registrars are in an optimum position to develop their newly acquired knowledge and skills to enhance training and intends to improve patient safety and satisfaction.

Tetrafurcation of the subscapular artery. Anatomical and clinical implications.

Anatomic variations of axillary artery branches are commonly encountered during radiological investigation and surgical operations. Their existence can confuse interpretation of radiological results and lead to undesired complications during surgery. In this report authors describe a rare case of a subscapular arterial trunk that gave origin to thoracodorsal, circumflex scapular, posterior humeral circumflex, and lateral thoracic artery. Such a variation might cause undesired sequelae during trauma management and a variety of common flap harvesting operations including latissimus dorsi, scapular and parascapular flaps. Furthermore it presents embryological interest as it gives insight to embryologic development of axillary area.

Complementary integrative approach for treating pruritus.

Complementary and alternative medicine (CAM) is a conservative and increasingly popular approach to treat pruritus for both patients and medical providers. CAM includes natural products, mind-body medicine, and manipulative and body-based practices. In this overview, we summarize current evidence, possible mechanisms and clinical approaches for treating pruritus with CAM techniques. We focus on pruritus associated with atopic dermatitis, herpes zoster, chronic urticaria, burns, and postoperative contexts where the evidence for CAM approaches is promising.

Genetic determinants of plasma ß2-glycoprotein I levels: a genome-wide association study in extended pedigrees from Spain.

BACKGROUND: ß2 -Glycoprotein I (ß2 -GPI), also designated apolipoprotein H, is a 50-kDa protein that circulates in blood at high concentrations, playing important roles in autoimmune diseases, hemostasis, atherogenesis, and angiogenesis, as well as in host defense against bacteria and in protein/cellular waste removal. Plasma ß2 -GPI levels have a significant genetic component (heritability of ~ 80%). OBJECTIVES: To present the results of a genome-wide association study for plasma ß2 -GPI levels in a set of extended pedigrees from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. PATIENTS/METHODS: A total of 306 individuals for whom ß2 -GPI plasma measurements were available were typed for 307,984 single-nucleotide polymorphisms (SNPs) with the Infinium 317k Beadchip (Illumina). Association with the ß2 -GPI phenotype was investigated through variance component analysis, and the most significant results were followed up for association with coronary artery disease (CAD) in an independent in silico analysis involving 5765 CAD cases from the PROCARDIS Project and 7264 controls from the PROCARDIS Project and the Wellcome Trust Case Control Consortium (WTCCC) collection. RESULTS: After correction for multiple testing, three SNPs located in/around two genes (ELF5 and SCUBE2) reached genome-wide significance. Moreover, an SNP in the APOH gene showed suggestive association with the ß2 -GPI phenotype. Some of the identified genes are plausible biological candidates, as they are actually or potentially involved in inflammatory processes. CONCLUSIONS: Our results represent a first step towards identifying common variants reflecting the genetic architecture influencing plasma ß2 -GPI levels, and warrant further validation by functional experiments, as the functions of some of the discovered loci are still unknown.

Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis: a patient- and examiner-blinded, randomized, placebo-controlled, crossover trial.

BACKGROUND: Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner-blinded, randomized, placebo-controlled, crossover trial. METHODS: Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. RESULTS: Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001). CONCLUSIONS: Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention.

Temperature modulated histamine-itch in lesional and nonlesional skin in atopic eczema - a combined psychophysical and neuroimaging study.

BACKGROUND: Itch is the major symptom of many allergic diseases; yet it is still difficult to measure objectively. The aim of this study was to use an evaluated itch stimulus model in lesional (LS) and nonlesional (NLS) atopic eczema (AE) skin and to characterize cerebral responses using functional magnetic resonance imaging (fMRI). METHODS: Thermal modulation was performed on a histamine stimulus in randomized order on LS or NLS in rapid alternating order from 32 degrees C (warm) to 25 degrees C (cold). Subjective itch ratings were recorded. Additionally, fMRI measurements were used to analyze the cerebral processing (n = 13). Healthy skin (HS) of age-matched volunteers served as control (n = 9). RESULTS: Mean VAS itch intensity was significantly (P < 0.0001) higher during the relative cold [55.2 +/- 8.3% (LS); 48.6 +/- 8.2% (NLS)] compared to the relative warm blocks [36.0 +/- 7.3% (LS); 33.7 +/- 7.6% (NLS)]. Compared to HS, the itch response was delayed in LS and NLS. Itch intensity was perceived highest in LS, followed by NLS and HS. For NLS, fMRI revealed at the beginning of the itch provocation a cerebral deactivation pattern in itch processing structures (thalamus, prefrontal, cingulate, insular, somatosensory and motor cortex). During the course of stimulation, the cerebral deactivation was reduced with time and instead an activation of the basal ganglia occurred. In contrast LS showed an activation instead of deactivation pattern already at the beginning of the stimulation in the above mentioned structures. CONCLUSIONS: Moderate short-term temperature modulation led to a reproducible, significant enhancement of histamine-induced itch with the strongest effect in LS. The differences in itch perception and itch kinetics between healthy volunteers and NLS in patients point towards an ongoing central inhibitory activity patients with AE, especially at the beginning of the itch provocation.

Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema - a blinded, randomized, placebo-controlled, crossover trial.

BACKGROUND: Itch is a major symptom of allergic skin disease. Acupuncture has been shown to exhibit a significant effect on histamine-induced itch in healthy volunteers. We investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double-blind, randomized, placebo-controlled, crossover trial. METHODS: An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before (direct effect) and after (preventive effect) two experimental approaches or control observation: acupuncture at points Quchi and Xuehai [verum acupuncture (VA), dominant side], 'placebo-point' acupuncture (PA, dominant side), no acupuncture (NA). Itch intensity was recorded on a visual analogue scale. After 10 min, wheal and flare size and skin perfusion (via LASER-Doppler) were measured at the stimulus site, and the validated Eppendorf Itch Questionnaire (EIQ) was answered. RESULTS: Mean itch intensity was significantly lower in VA (35.7 +/- 6.4) compared to NA (45.9 +/- 7.8) and PA (40.4 +/- 5.8) regarding the direct effect; and significantly lower in VA (34.3 +/- 7.1) and PA (37.8 +/- 5.6) compared to NA (44.6 +/- 6.2) regarding the preventive effect. In the preventive approach, mean wheal and flare size were significantly smaller in VA (0.38 +/- 0.12 cm(2)/8.1 +/- 2.0 cm(2)) compared to PA (0.54 +/- 0.13 cm(2)/13.5 +/- 2.8 cm(2)) and NA (0.73 +/- 0.28 cm(2)/15.1 +/- 4.1 cm(2)), and mean perfusion in VA (72.4 +/- 10.7) compared to NA (84.1 +/- 10.7). Mean EIQ ratings were significantly lower in VA compared to NA and PA in the treatment approach; and significantly lower in VA and PA compared to NA in the preventive approach. CONCLUSIONS: Acupuncture at the correct points showed a significant reduction in type I hypersensitivity itch in patients with atopic eczema. With time the preventive point-specific effect diminished with regard to subjective itch sensation, whereas it increased in suppressing skin-prick reactions.

Eighteen-month results of a randomized prospective study comparing transurethral photoselective vaporization with transvesical open enucleation for prostatic adenomas greater than 80 cc.

CONFLICT OF INTEREST: None Take Home Message: This is a prospective randomized study showing that for large prostatic adenomas, photoselective vaporization of the prostate requires less blood transfusions, shorter catheterization time and shorter hospital stay compared to open prostatectomy, while achieving similar functional results at the same time. AIM: The effectiveness and the safety of photoselective vaporization of the prostate (PVP) was compared to that of open prostatectomy (OP) for the surgical treatment of large prostatic adenomas. METHODS: 125 patients with prostate glands>80 ml, were randomly allocated to PVP (n=65) or OP (n=60) and prospectively evaluated at 1, 3, 6, 12, and 18 months postoperatively. International prostate symptom score (IPSS) and peak urinary flow rate (Qmax) were chosen as primary treatment-related endpoints. RESULTS: Longer length of operation time, shorter length of catheterization and hospital stay were experienced by patients who underwent PVP. Although patients who underwent OP showed a higher transfusion rate, adverse events in general were minor and of similar profile in both groups. All functional parameters improved significantly compared to baseline values in both groups. There was no difference in IPSS between the two groups at 3, 6, 12, and 18 months postoperatively. Patients who underwent OP scored better in the IPSS-Quality of life score at 18 months postoperatively. At 18 months there were no significant differences between the two groups in the Qmax, post void residual urine volume and in the International Index for Erectile function-5 questionnaire. At three months prostate volume was significantly lower in the OP group and remained as such throughout follow-up. CONCLUSIONS: Our results indicate that for an 18 month period photoselective vaporization of the prostate is a highly acceptable treatment alternative to open prostatectomy.

How many populations set foot through the Patagonian door? Genetic composition of the current population of Bahía Blanca (Argentina) based on data from 19 Alu polymorphisms.

The city of Bahía Blanca occupies a strategic place in Argentina south of the Pampean region in the north-east corner of the Patagonia. Since 1828, this city has been the historical and political border between Amerindian lands in the south, and the lands of European colonists. Nowadays, Bahía Blanca is an urban population mainly composed by descendents of immigrants from Spain and other European countries with apparently low admixture with Amerindians. In view of the unexpectedly high Amerindian admixture levels (about 46.7%) suggested by mtDNA data, and protein markers (19.5%), we analyzed a set of 19 Alu polymorphisms (18 autosomal, 1 of Chromosome Y) in a well-documented genealogical sample from Bahía Blanca. The genotyped sample was made up of 119 unrelated healthy individuals whose birth place and grandparent origins were fully documented. According to available genealogical records, the total sample has been subdivided into two groups: Bahía Blanca Original (64 individuals with all 4 gandparents born in Argentina) and Bahía Blanca Mix (55 individuals with one to three grandparents born out of Argentina). Allele frequencies and gene diversity values in Bahía Blanca fit well into the European ranges. Population relationships have been tested for 8 Alu markers, whose variation has been described in several Amerindian and European samples. Reynolds genetic distances underline the significant genetic similarity of Bahía Blanca to Europeans (mean distance 0.044) and their differentiation from Amerindians (0.146). Interestingly enough, when the general sample is divided, Bahía Blanca Original appears slightly closer to Amerindians (0.127) in contrast to Bahía Blanca Mix (0.161). Furthermore, the genetic relationships depicted through a principal components analysis emphasize the relative similarity of Bahía Blanca Original to Amerindians. A thorough knowledge of the sample origins has allowed us to make a subtle distinction of the genetic composition of Bahía Blanca.

Erythema multiforme due to contact with laurel oil.

Erythema multiforme is a relatively common skin disorder. The best known cause is herpes simplex virus infection. We report the first case of erythema multiforme due to contact with laurel oil. The diagnosis was confirmed by the positive patch test to laurel oil, the histopathological studies of the lesions and the histopathological studies of the positive patch test to laurel oil.

Involvement of NK cells against tumors and parasites.

Host resistance against pathogens depends on a complex interplay of innate and adaptive immune mechanisms. Acting as an early line of defence, the immune system includes activation of neutrophils, tissue macrophages, monocytes, dendritic cells, eosinophils and natural killer (NK) cells. NK cells are lymphoid cells that can be activated without previous stimulation and are therefore like macrophages in the first line of defence against tumor cells and a diverse range of pathogens. NK cells mediate significant activity and produce high levels of proinflammatory cytokines in response to infection. Their cytotoxicity production is induced principally by monocyte-, macrophage- and dendritic cell-derived cytokines, but their activation is also believed to be cytokine-mediated. Recognition of infection by NK cells is accomplished by numerous activating and inhibitory receptors on the NK cells' surface that selectively trigger the cytolytic activity in a major histocompability complex-independent manner. NK cells have trypanocidal activity of fibroblast cells and mediate direct destruction of extracellular epimastigote and trypomastigote forms of T. cruzi and T. lewisi in vitro; moreover, they kill plasmodia-infected erythrocytes directly through cell-cell interaction. This review provides a more detailed analysis of how NK cells recognize and respond to parasites and how they mediate cytotoxicity against tumor cells. Also the unique role of NK cells in innate immunity to infection and the relationship between parasites and carcinogenesis are discussed.