Characterization of the human ridged and non-ridged skin: a comprehensive histological, histochemical and immunohistochemical analysis.

The structure of the human skin is directly dependent on its location and the mechanical forces to which it is subjected. In the present work, we have performed a comprehensive analysis of the human ridged and non-ridged skin to identify the differences and similarities between both skin types. For this purpose, human skin samples were obtained from dorsal hand skin (DHS), palmar hand skin (PHS), dorsal foot skin (DFS) and plantar foot skin (PFS) from the same cadaveric donors. Histological, histochemical and semiquantitative and quantitative immunohistochemical analyses were carried out to evaluate the epidermis, dermis and basement membrane. Results show that the epithelial layer of ridged skin had larger cell number and size than non-ridged skin for most strata. Melanocytes and Langerhans cells were more abundant in non-ridged skin, whereas Merkel cells were preferentially found in ridged skin. The expression pattern of CK5/6 was slightly differed between non-ridged and ridged skin. Involucrin expression was slightly more intense in non-ridged skin than in ridged skin. Collagen was more abundant in foot skin dermis than in hand skin, and in ridged skin as compared to non-ridged skin. Elastic fibers were more abundant in DHS. Biglycan was more abundant in foot skin than in hand skin. No differences were found for blood and lymphatic vessels. The basement membrane laminin was preferentially found in foot skin. These results revealed important differences at the epithelial, dermal and basement membrane levels that could contribute to a better knowledge of the human skin histology.

Short communication: grazing pattern of dairy cows that were selected for divergent residual feed intake as calves.

The aim of this study was to investigate and assess differences in the grazing pattern of 2 groups of mature dairy cows selected as calves for divergent residual feed intake (RFI). Sixteen Holstein-Friesian cows (471±31kg of body weight, 100 d in milk), comprising 8 cows selected as calves (6-8 mo old) for low (most efficient: CSCLowRFI) and 8 cows selected as calves for high (least efficient: CSCHighRFI) RFI, were used for the purpose of this study. Cows (n=16) were managed as a single group, and strip-grazed (24-h pasture allocation at 0800h) a perennial ryegrass sward for 31 d, with measurements taken during the last 21 d. All cows were equipped with motion sensors for the duration of the study, and jaw movements were measured for three 24-h periods during 3 random nonconsecutive days. Measurements included number of steps and jaw movements during grazing and rumination, plus fecal particle size distribution. Jaw movements were analyzed to identify bites, mastication (oral processing of ingesta) during grazing bouts, chewing during rumination, and to calculate grazing and rumination times for 24-h periods. Grazing and walking behavior were also analyzed in relation to the first meal of the day after the new pasture was allocated. Measured variables were subjected to multivariate analysis. Cows selected for low RFI as calves appeared to (a) prioritize grazing and rumination over idling; (b) take fewer steps, but with a higher proportion of grazing steps at the expense of nongrazing steps; and (c) increase the duration of the first meal and commenced their second meal earlier than CSCHighRFI. The CSCLowRFI had fewer jaw movements during eating (39,820 vs. 45,118 for CSCLowRFI and CSCHighRFI, respectively), more intense rumination (i.e., 5 more chews per bolus), and their feces had 30% less large particles than CSCHighRFI. These results suggest that CSCLowRFI concentrate their grazing activity to the time when fresh pasture is allocated, and graze more efficiently by walking and masticating less, hence they are more efficient grazers than CSCHighRFI.

Incorporating a prediction of postgrazing herbage mass into a whole-farm model for pasture-based dairy systems.

The DairyNZ whole-farm model (WFM; DairyNZ, Hamilton, New Zealand) consists of a framework that links component models for animal, pastures, crops, and soils. The model was developed to assist with analysis and design of pasture-based farm systems. New (this work) and revised (e.g., cow, pasture, crops) component models can be added to the WFM, keeping the model flexible and up to date. Nevertheless, the WFM does not account for plant-animal relationships determining herbage-depletion dynamics. The user has to preset the maximum allowable level of herbage depletion [i.e., postgrazing herbage mass (residuals)] throughout the year. Because residuals have a direct effect on herbage regrowth, the WFM in its current form does not dynamically simulate the effect of grazing pressure on herbage depletion and consequent effect on herbage regrowth. The management of grazing pressure is a key component of pasture-based dairy systems. Thus, the main objective of the present work was to develop a new version of the WFM able to predict residuals, and thereby simulate related effects of grazing pressure dynamically at the farm scale. This objective was accomplished by incorporating a new component model into the WFM. This model represents plant-animal relationships, for example sward structure and herbage intake rate, and resulting level of herbage depletion. The sensitivity of the new version of the WFM was evaluated and then the new WFM was tested against an experimental data set previously used to evaluate the WFM and to illustrate the adequacy and improvement of the model development. Key outputs variables of the new version pertinent to this work (milk production, herbage dry matter intake, intake rate, harvesting efficiency, and residuals) responded acceptably to a range of input variables. The relative prediction errors for monthly and mean annual residual predictions were 20 and 5%, respectively. Monthly predictions of residuals had a line bias (1.5%), with a proportion of square root of mean square prediction error (RMSPE) due to random error of 97.5%. Predicted monthly herbage growth rates had a line bias of 2%, a proportion of RMSPE due to random error of 96%, and a concordance correlation coefficient of 0.87. Annual herbage production was predicted with an RMSPE of 531 (kg of herbage dry matter/ha per year), a line bias of 11%, a proportion of RMSPE due to random error of 80%, and relative prediction errors of 2%. Annual herbage dry matter intake per cow and hectare, both per year, were predicted with RMSPE, relative prediction error, and concordance correlation coefficient of 169 and 692kg of dry matter, 3 and 4%, and 0.91 and 0.87, respectively. These results indicate that predictions of the new WFM are relatively accurate and precise, with a conclusion that incorporating a plant-animal relationship model into the WFM allows for dynamic predictions of residuals and more realistic simulations of the effect of grazing pressure on herbage production and intake at the farm level without the intervention from the user.

The relationship between milk production and farm-gate nitrogen surplus for the Waikato region, New Zealand.

As the scope and scale of New Zealand (NZ) dairy farming increases, farmers and the industry are being challenged by Government and the New Zealand public to address growing environmental concerns. Dairying has come under increasing scrutiny from local authorities tasked with sustainable resource management. Despite recent efforts of farmers and industry to improve resource use efficiency, there is increasing likelihood of further regulatory constraints on water use and nutrient management. This study uses available data on farm-gate nitrogen (N) surpluses and milk production from the Waikato, New Zealand's largest dairying region, together with a farm scale modeling exercise, to provide a perspective on the current situation compared to dairy farms in Europe. It also aims to provide relevant guidelines for N surpluses and efficiencies under NZ conditions. Waikato dairy farms compare favorably with farms in Europe in terms of N use efficiency expressed as L milk/kg farm-gate N surplus. Achievable and realistic good practice objectives for Waikato dairy farmers could be 15,000 L milk/ha (1200 kg milk fat plus protein/ha) with a farm-gate N surplus of 100 kg/ha giving an eco-efficiency (L milk/kg N surplus) of 150, and long-term average nitrate leaching losses of approximately 25-30 kg/ha/yr. This can be achieved by increasing the N conversion efficiency through lower replacement rates (16 versus 22%), lower stocked (< 3 cows/ha) high genetic merit cows (30 L milk/day at peak) milked for longer (277 versus 240 days), feeding effluent-irrigated, home-grown, low-protein supplements to cows on high-protein, grass-clover pastures to dilute N concentration in the diet, removing some of the urinary N from the paddocks during critical times by standing cows on a loafing pad for part of the day, and through lower N fertilizer rates (50-70 kg/ha/yr compared to the norm of 170-200 kg/ha/yr) and using a nitrification inhibitor and gibberellins to boost pasture growth and the former to reduce N leaching.

Perioperative anesthetic management of reductive glossoplasty in a patient with Beckwith-Wiedemann syndrome. / Manejo anestésico perioperatorio de glosoplastia reductora en paciente con síndrome de Beckwith-Wiedemann.

INTRODUCTION: Postoperative management of patients with the congenital growth disorder Beckwith-Wiedemann syndrome (BWS) can be complicated. The main clinical manifestations of the syndrome are macroglossia - which may hamper airway management -, prematurity, hemihypertrophy, omphalocele, embryonal tumours and episodes of neonatal hypoglycaemia. OBJECTIVE: Our main objective is to describe the perioperative management and potential anaesthetic complications in paediatric patients with BWS undergoing glossectomy. METHODS: Case report and literature review. RESULTS: We describe the case of an 11-month-old patient diagnosed with BWS who underwent reduction glossoplasty. We performed a comprehensive preoperative evaluation, taking into account potential anaesthetic complications derived from both macroglossia and prematurity, and the risk of hypoglycaemia. The procedure was performed under general anaesthesia. Intubation - performed according to difficult airway management algorithms - was uneventful and the patient was successfully extubated in the operating room. The patient remained stable during the postoperative period, with good respiratory dynamics, SatO2>96% and good glycaemic control. Oral intake was started 4hours after surgery, and she was discharged to the ward at 24hours. CONCLUSION: BWS patients require a multimodal approach that includes detailed preoperative planning and knowledge of potential airway-related and systemic complications.

[Gonococcal pelviperitonitis: a diagnostic challenge].

Neisseria gonorrhoeae is the second most common etiological agent of pelvic inflammatory disease and is currently un-derdiagnosed due to its asymptomatic presentation in 50% of cases. When the disease presents, it may appear in the form of acute abdomen and normal imaging tests, making it a major diagnostic challenge. We present four cases of acute gonococcal peritonitis. The main symptom was acute abdominal pain, and both the gy-necological examination and complementary tests showed normal results. The only notable finding from the laparoscopy was the existence of purulent ascitic fluid. The results of the anatomical and pathological tests were all normal. Endocer-vical and ascitic fluid culture showed infection with N. gonorrhoeae, and in one case, concomitant infection with Chlamydia trachomatis. The definitive treatment applied was intravenous antibiotic therapy. When a sexually active young woman is diagnosed with peritonitis that has no apparent cause, it is important to rule out sexually transmitted diseases.

Technical note: a simple model to estimate changes in dietary composition of strip-grazed cattle during progressive pasture defoliations.

Methodological problems occur in measuring herbage intake and diet quality during short-term (4-24h) progressive defoliations by grazing. Several models were developed to describe pasture component selection by grazing ruminants, particularly sheep. These models contain empirical coefficients to determine preferences that require laborious and data-demanding calibration. The objective was to develop a simple and practical model of changes in diet composition (green:dead) of pastures strip-grazed by dairy cows. The model was based on 3 premises when cows are strip-grazed in relatively homogeneous swards: 1) cows eat dead material only when green leaf and uncontaminated material have been removed; 2) dead material increases toward the bottom of the sward canopy; and 3) cows progressively defoliate pasture in layers. The main simplification in this model was assuming a linear decrease of green mass from the top to the bottom of the sward canopy. Thus, the proportion of green mass in the stratum eaten depended on the proportion of green in the entire sward canopy and its vertical profile. The model offers a simple solution to estimate changes in dietary compositions in pastures strip-grazed by dairy cattle during progressive pasture defoliations. It uses 2 inputs, the green mass proportion of the total herbage mass and the proportion of total herbage mass eaten during grazing. This can be optionally complemented with inputs of herbage chemical composition. The main outputs of the model are the proportions of green and dead herbage mass in the diet. For example, if the green proportion in the sward was 0.5 and the proportion of herbage mass eaten was 0.5, then the diet would be 0.75 green:0.25 dead; assuming 0.8 and 0.4 digestibility for green and dead material, respectively, the diet digestibility would be 0.7.

A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.

OBJECTIVE: To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT). DESIGN: A randomised, open-label trial. MATERIAL AND METHODS: In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months. RESULTS: During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group. CONCLUSIONS: Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.

Restricting time at pasture: effects on dairy cow herbage intake, foraging behavior, hunger-related hormones, and metabolite concentration during the first grazing session.

This study investigated the effect of restricting grazing time on circulating concentrations of ghrelin, nonesterified fatty acids (NEFA), and glucose before, and foraging behavior of dairy cows during, the first grazing session of the day (GS, 0800-1200 h). Forty-eight Holstein-Friesian cows (470 +/- 47 kg of BW; 35 +/- 9 d in milk) were strip-grazed on a perennial ryegrass pasture for either 4 h after each milking (2 x 4), 8 h between milkings (1 x 8), or the 24-h period excluding milking times (CTL). Cows were bled before the GS; plasma was analyzed for ghrelin and serum for glucose and NEFA. Herbage mass was measured pregrazing (0730 h), during and at the end of the GS (1200 h), and postgrazing (24 h after the first measurement). Herbage mass data were fitted to a model to estimate herbage disappearance rates. Herbage intake and bite mass were calculated using herbage mass disappearance and behavioral measurements. Bite rate, eating, searching, ruminating, and idling time were determined during the GS for each cow. No difference in glucose concentration was found between treatments. Concentrations of NEFA and ghrelin were the greatest for cows in the 1 x 8 treatment. Daily herbage intake did not differ between treatments; however, during the GS 1 x 8 had a greater herbage intake than 2 x 4 and CTL. Bite mass differed between treatments and throughout the GS. Bite mass was smallest for CTL during the first 60 min and greatest during the last 90 min, when cows in the 2 x 4 treatment had the smallest bite mass. Cows in 1 x 8 spent the longest time eating and the least time searching and ruminating. Eating time was greatest for 1 x 8 during the first 60 and last 90 min of the GS. Searching time only differed in the second 60 min, when it was the lowest for 1 x 8. Cows from all treatments did not ruminate during the first 120 min. Cows in CTL had the greatest rumination time during the last 90 min. The model fitted to represent dynamics of herbage mass disappearance presented differences in the fractional herbage disappearance rate. There was an interaction between treatment and time in herbage depletion rate. The results of this study present a fuller picture of foraging dynamics during the first 4 h of grazing and its potential relationship with physiological markers of hunger as affected by grazing management.

Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma.

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ±â€¯1.89 µm rendering them suitable for intravitreal injection using conventional 25G-32G needles. >62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00 ±â€¯0.94 mM versus 6.89 ±â€¯0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single-drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma.