Macroscopic Pathology Research Articles

Searching cause of death through different autopsy methods: A new initiative.

A lawful disposal of human dead body is only possible after establishment of proper and valid cause of death. If the cause is obscure, autopsy is the only mean of search. Inadequacy and unavailability of health care facility often makes this situation more complicated in developing countries where many deaths remain unexplained and proper mortality statistics is missing, especially for infant and children. Tissue sampling by needle autopsy or use of various imaging technique in virtopsy have been tried globally to find out an easier alternative. An exclusive and unique initiative, by limited autopsy through tissue biopsy and body fluid analysis, has been taken to meet this dire need in African and some of Asian developing countries, as worldwide accepted institutional data are even missing or conflicting at times. Traditional autopsy has changed little in last century, consisting of external examination and evisceration, dissection of organs with identification of macroscopic pathologies and injuries, followed by histopathology. As some population groups have religious objections to autopsy, demand for minimally invasive alternative has increased of late. But assessment of cause of death is most important for medico-legal, epidemiological and research purposes. Thus minimally invasive technique is of high importance in primary care settings too. In this article, we have made a journey through different autopsy methods, their relevance and applicability in modern day perspective considering scientific research articles, textbooks and interviews.

Is there a difference between the right and left kidney? A macroscopic approach in Brazilian Shorthair Cat

ABSTRACT The aim of this study was to characterize the renal morphology and anatomical variations of the renal pedicle in domestic shorthaired cats. Dissections were performed in 40 adult cats, obtained from the necropsy unit without macroscopic renal pathology. Kidney dimensions (length, width, and thickness) and the length and origin of the renal arteries and main branches were measured. The length, width and thickness of the right kidney (cm) were 3.83±0.46, 2.42±0.22, and 2.22±0.33 in males, and 3.61±0.53, 2.28±0.38, and 2.13±0.40 in females, respectively. In the left kidney, these measures were 3.82±0.32, 2.48±0.31, and 2.37±0.32 in males, and 3.48±0.47, 2.39±0.26, and 2.15±0.34 in females, respectively. The left kidneys of males were significantly bigger than those of females. There was a positive linear correlation between the rostrum-sacral length and ellipsoid volume of the left kidney only in males. Most of the kidneys were situated ventrally between the third to fifth lumbar vertebras. The right renal artery was situated ventrally to third lumbar vertebra and the left artery to the fourth. The results of the present study contribute to the field of comparative and applied anatomy.

Trunnion Corrosion and Early Failure in Monolithic Metal-on-Polyethylene TMZF Femoral Components: A Case Series

We describe four patients who were treated with primary total hip arthroplasty (THA) at two tertiary academic Australian teaching hospitals that experienced premature failure of head-neck trunnions through dissociation of the head-neck taper junction. This retrospective case series have similar clinical presentations and macroscopic pathology with severe head-neck taper junction loss of material, corrosion and early catastrophic failure. It is proposed that the accelerated wear is related to use of varus offset neck in a proprietary beta titanium alloy (Ti-12Mo-6Zr-2Fe or TMZFÒ Stryker Osteonics, Mahwah NJ, USA) TMZF femoral stem, longer head-neck combination in a relatively active, older, male patient population. In this limited case series presentation was on average 80 months (range 53-92) following index procedure. In three of the four patients, a prodromal period of groin or buttock pain was reported for between 1 week and 2 months prior to acute presentation. Significant metallosis and local tissue damage including gluteal muscle insufficiency was evident. Each stem revised was well fixed. An extended trochanteric osteotomy was required in two of the four cases for stem extraction. We recommend caution and further evaluation on the relationship between TMZF metal alloy and its longevity in higher demand patients with high neck offset, varus stem geometry and large CoCr bearing heads.

Tips for a Flipped Classroom: What We Wished We Knew Before We Flipped

This article was migrated. The article was marked as recommended. The flipped classroom approach has been used in health profession education to encourage active learning, but predominantly pre-learning flipped activities are passive knowledge input, such as watching recorded lectures. To encourage active learning, online learning activities focusing on knowledge acquisition and application were developed as pre-work for the flipped classroom in a pathology course in an undergraduate medical programme. These included labeling macroscopic pathology and histology images, case scenarios and multiple-choice questions. Student responses indicated that some of these were helpful, while some interfered with learning.In addition to the pedagogical issues associated with designing a flipped classroom, instructors also need to consider the technical elements of designing pre-course material for independent study. This paper examines the components of this flipped classroom's pre-work and highlights successful and unsuccessful e-learning components.

The TAM receptors Axl and Mer play a joint-specific protective role in experimental arthritis

Abstract Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by an unrestrained inflammatory response in synovial joints. One family of tyrosine kinase receptors involved in anti-inflammatory feedback mechanism are Tyro3, Axl and Mer (TAM). The plasma level of the TAM receptor ligand Gas6 is significantly reduced in RA patients suggesting this feedback mechanism is impaired in RA. We investigated the individual role of each TAM receptor in experimental arthritis. Methods The KRN serum transfer model of arthritis was induced by two intraperitoneal injections of arthritic K/BxN serum in TAM receptor single gene knock-out mice (Tyro3−/−, Axl−/−, Mer−/−) and wild-type (WT) mice. Ankle joints were macroscopically scored for 7 days and knee and ankle joints were taken at the end of the experiment for histology and immunohistochemistry. Results Mer−/− mice had an increased macroscopic ankle score until day 4 whereas Axl−/− mice had an enhanced macroscopic score from day 4 until the end of the experiment. Histology of the ankle joints showed significantly increased arthritis pathology in Axl−/− mice compared to WT. In contrast, enhanced macroscopic score and arthritis pathology in the knee joints of Mer−/− mice was observed. Both in ankle and knee joints, no protective or aggravating role of Tyro3 was seen. To explain the discrepancy of Axl involvement between ankle and knee, we looked for Axl expression in synovium of naïve mice. The lining layer of ankle synovium was completely Axl-positive whereas only mild expression in the knee joints was observed. Conclusion These findings identify the TAM receptors Axl and Mer as important protective players in arthritis in addition to being expressed in a joint-specific manner.

Imaging, biodistribution, and toxicology evaluation of 212Pb-TCMC-trastuzumab in nonhuman primates

IntroductionThe biodistribution and toxicology of a radiotherapeutic 212Pb-trastuzumab conjugate were evaluated in nonhuman primates to meet the investigational new drug requirements prior to a phase I clinical trial in human subjects. MethodsMale cynomolgus monkeys (n=3/group) were injected intraperitoneally with the 212Pb-trastuzumab conjugate and terminated at 8h, 10d, and 90d post-injection. Quantitative imaging studies in phantoms and monkeys were conducted using a planar gamma camera and a high purity germanium (HPGe) detector out to 48h following injection. Biodistribution analyses were conducted at 8h; all tissues and time points were evaluated for macroscopic and microscopic pathology. Blood samples were taken throughout the 90d study period for assessment of hematology parameters and serum chemistry parameters. ResultsQuantitative gamma camera imaging and region-of-interest analyses of phantoms and monkeys indicated that 95.5±5.0% of the decay-corrected 212Pb activity was retained in the peritoneal region up to 48h following administration of the 212Pb-trastuzumab. Gamma-ray spectroscopy analyses confirmed that 87.6±4.5% of the decay-corrected 212Bi activity was also retained in the peritoneal cavity during this time. Serum chemistry parameters for all groups always fell within normal ranges. Gross and histopathology evaluations showed no radiation-related toxicity in any tissue at any time. ConclusionIn vivo imaging and biodistribution analyses showed that about 90% of both 212Pb and decay product 212Bi remained in the monkey peritoneal cavity. The imaging methods could also be applied to human subjects. The lack of toxicity observed in monkeys following intraperitoneal injection of the 212Pb-trastuzumab conjugate supports its clinical assessment in humans.

The association between healed skeletal fractures indicative of interpersonal violence and alcoholic liver disease in a cadaver cohort from the Western Cape, South Africa.

Interpersonal violence (IPV) and heavy alcohol consumption are major problems in the Western Cape Province of South Africa. Cranio-maxillofacial fractures, particularly nasal and zygomatic bone fractures, as well as isolated radial fractures (Colles fractures) and ulnar shaft fractures (parry fractures), are indicative of IPV, while alcoholic liver disease (ALD) is the consequence of chronic alcohol abuse. We therefore aim to investigate whether a significant association exists between the prevalence of cranio-maxillofacial fractures and parry fractures and ALD in a Western Cape population. Embalmed cadavers (n=124) used for medical students' anatomy training at the Division of Anatomy and Histology, Faculty of Medicine and Health Sciences, Stellenbosch University were studied. The cadavers were dissected according to departmental protocol. The liver of each cadaver was investigated for macroscopic pathology lesions. Tissue samples were removed, processed to wax, and sectioned and stained with hematoxylin and eosin (H&E). All soft tissue was removed from the skulls, radii, and ulnae, which were then investigated for healed skeletal trauma. The results showed 37/124 (29.8%) cadavers had healed cranio-maxillofacial fractures and 24/124 (19.4%) cadavers had morphologic features of ALD. A total of 12/124 (9.7%) cadavers showed signs of both ALD and healed cranio-maxillofacial trauma. More males were affected than females, and left-sided facial fractures were statistically more common compared to the right side. This study illustrated a significant trend between alcohol abuse and cranio-maxillofacial fractures in individuals from communities with a low socio-economic status (SES) where IPV is a major problem.

Repeated high-dose (5 × 108 TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits

ABSTRACTConcern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×108 TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×108 TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×108 TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

Angioscopy in 2015: the Role of Macroscopic Pathology in Living Patients

Angioscopy can detect lipid-rich yellow plaques that are regarded as vulnerable plaques. The patients who have multiple yellow plaques are regarded as vulnerable patients. The disrupted plaques can also be visualized directly by angioscopy, but they can be detected more sensitively as the presence of thrombus. On the other hand, angioscopy can also evaluate the neointima formed over stents. The follow-up angioscopic examinations after the implantation of coronary stents visualized atherosclerosis progression as the formation of yellow plaque in the stent-implanted segments. Recently, the presence of yellow plaque at 1 year after stent implantation has been demonstrated to be the risk of future stent failure. Atherosclerosis progression shown by the formation of yellow plaque may be the major mechanism and “final common pathway” for the very-late stent failure.

Bandscheibenveränderungen des Hundes in der bildgebenden Diagnostik

Intervertebral disc degeneration can cause intervertebral disc herniation. Diagnostic imaging, including radiography, computed tomography and magnetic resonance imaging, is the most important tool in diagnosis. Firstly, an overview of macroscopic and biochemical physiology and pathology of the intervertebral disc will be given. Subsequently, the physics of diagnostic imaging and the appearance of intervertebral disc degeneration and displacement in several imaging methods are described.

Anatomical distribution and gross pathology of wounds in necropsied farmed mink (Neovison vison) from June and October.

BackgroundWounds are regarded as an indicator of reduced welfare in mink production; however, information on the occurrence and significance of wounds is sparse. To provide a basis for assessment and classification of wounds in farmed mink, the distribution pattern and characteristics of wounds in farmed mink in June and October, respectively, is described. A total of 791 and 660 mink from 6 to 12 Danish mink farms, respectively, were examined. The mink were either found dead or were euthanized due to injury or other disease. Mink included from June were kits in the pre-weaning and weaning period (1–2 months old). Mink included from October were juveniles in the late growth period (approximately 5–6 months old) or older. Macroscopic pathology and wound location was systematically recorded.ResultsThere was considerable variation in morphology as well as location of wounds between June and October. Wounds were primarily located on the front parts of the body and in the head in June (1–2 month old kits) and mainly on the rear parts of the body and on the tail in October (5–6 month old kits and older). Moreover, there were significantly more females than males with wounds for most wound types, and significant differences in occurrence of ear and tail base wounds between certain colour types.ConclusionsWounds varied significantly from June to October with respect to morphology and anatomical location. Wounds in June were primarily located on the front parts of the body and in the head, while wounds in October were mainly present on the hind parts of the body and on the tail. The majority of the wounds were found in specific well defined skin areas and could therefore be grouped into categories according to anatomical location.

Gene expression profiling in non-human primate jejunum, ileum and colon after total-body irradiation: a comparative study of segment-specific molecular and cellular responses.

BackgroundAlthough extensive studies have investigated radiation-induced injuries in particular gastrointestinal (GI) segments, a systematic comparison among the different segments on the basis of mode, magnitude and mechanism has not been reported. Here, a comparative study of segment-specific molecular and cellular responses was performed on jejunum, ileum and colon obtained at three time points (4, 7 and 12 days after irradiation) from non-human primate (Rhesus macaque) models exposed to 6.7 Gy or 7.4 Gy total body irradiation (TBI).ResultsPathway analysis on the gene expression profiles identified radiation-induced time-, dose- and segment-dependent activation of tumor necrosis factor α (TNFα) cascade, tight junction, apoptosis, cell cycle control/DNA damage repair and coagulation system signaling. Activation of these signaling pathways suggests that colon sustained the severest mucosal barrier disruption and inflammation, and jejunum the greatest DNA damage, apoptosis and endothelial dysfunction. These more pronounced alterations correlate with the high incidence of macroscopic pathologies that are observed in the colon after TBI. Compared to colon and jejunum, ileum was resistant to radiation injury. In addition to the identification a marked increase of TNFα cascade, this study also identified radiation induced strikingly up-regulated tight junction gene CLDN2 (196-fold after 7.4-Gy TBI), matrix degradation genes such as MMP7 (increased 11- and 41-fold after 6.7-Gy and 7.4-Gy TBI), and anoikis mediated gene EDA2R that mediate mucosal shedding and barrier disruption.ConclusionsThis is the first systematic comparative study of the molecular and cellular responses to radiation injury in jejunum, ileum and colon. The strongest activation of TNFα cascades and the striking up-regulation of its down-stream matrix-dissociated genes suggest that TNFα modulation could be a target for mitigating radiation-induced mucosal barrier disruption.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2168-y) contains supplementary material, which is available to authorized users.

Matrix changes due to the toxic effects of metronidazole in intestinal tissue of fish (Onchorhynchus mykiss).

Metranidazole (MTZ) is an antibiotic used for parasitic infections in a number of species. Accumulation of this drug in the environment and its interaction with fish of economic value makes this drug particularly important. In the present study, we examined the histopathological effects of MTZ on the intestinal tissue of Oncorhynchus mykiss. The fish in aquarium were exposed to MTZ at doses of 5, 10, 20 mg/L for 2, 4 and 8 days. At the end of the experiments, macroscopic pathology or death were not observed at these doses. Histochemical staining with Haematoxylene-Eosin, Periodic Acid Schiff and Gomori Trichrome showed, depending on increased dose and prolonged duration, areas of necrosis, edema, inflammation, small tears at the tips of the villi and excretion with heterogenic distribution of the Goblet cells. Moreover, changes in the connective tissue of the intestines due to toxicity of MTZ and decreases in immunostaining of matrix proteins such as laminin and collagen IV, especially in the epithelium were observed. Findings of the present study would be useful to demonstrate the adverse effects of MTZ use, emphasizing the importance of the effect on fish which could be very important public health.

Buried Adenocarcinoma Masquerading as a Refractory Rectal Stricture

45 year old African American female with a long standing history of Crohn's colitis (involving the descending and sigmoid colon with perianal fistulas) and medication non-compliance presented with worsening constipation for months. Patient was not on medications at the time of presentation, but has a history of treatment with asacol, azathioprine and infliximab. Patient denied fevers, nausea, vomiting or rectal bleeding. Colonoscopy revealed a 5 cm long tight rectal stricture about 10 cm from the anal verge along with extensive pan colitis and normal small bowel. Biopsy of the stricture revealed inflammatory infiltrate. MR enterogram revealed a tight rectal stricture with enhancement indicating inflammation. Patient was treated with high doses of prednisone followed by infliximab infusions along with endoscopic dilations to which she had minimal response. This was followed by injection to infliximab directly into the rectal stricture with limited response. Patient was referred for surgery where she underwent abdominal perineal resection of rectum with end-colostomy. The stricture appeared benign on macroscopic examination but pathology reports revealed intra-strictural adenocarcinoma and normal overlying mucosa. She had to undergo repeat surgery for complete resection followed by radiation and chemotherapy. Discussion: The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is well-known and has been widely described in literature. The risk of malgnancy is directly related to the severity of perianal involvement, extent of disease and its time course. In CD the risk is estimated to be around 30% after 25 years of diagnosis and noted to be higher in patients who receive the diagnosis before the age of 30. Our patient had long standing crohn's colitis, which was uncontrolled due to medication non-compliance. In addition, she was a smoker which increases the risk of malignancy. The stricture was biopsied multiple times on endoscopy and imaged with MR enterogram, which failed to reveal malignancy. Even during surgery, the surgeon did not suspect malignancy on gross examination as the mucosa appeared normal. The pathology specimen (see figure) demonstrates buried glands with adenocarcinoma interspersed within the stricture. Overlying mucosa appears normal. This is the first report where we describe a case of adenocarcinoma buried within the stricture with normal overlying mucosa. It is important for clinicians to have a high suspicion of malignancy in strictures which fail to respond to intensive therapy.Figure 1Figure 2Figure 3

Androgen actions via androgen receptor promote PTEN inactivation induced uterine cancer.

Haploinsufficient inactivating phosphatase and tensin homolog (Pten) mutations cause Cowden syndrome, an autosomal dominant risk genotype for hormone dependent reproductive cancers. As androgen actions mediated via the androgen receptor (AR) supports uterine growth and may modify uterine cancer risk, we hypothesized that a functional AR may increase PTEN inactivation induced uterine cancer. To test the hypothesis, we compared the PTEN knockout (PTENKO) induced uterine pathology in heterozygous PTENKO and combined heterozygous PTEN and complete AR knockout (PTENARKO) female mice. PTENKO induced uterine pathology was significantly reduced by AR inactivation with severe macroscopic uterine pathology present in 21% of PTENARKO vs 46% of PTENKO at a median age of 45 weeks. This could be due to reduced stroma ERα expression in PTENARKO compared to PTENKO uterus, while AR inactivation did not modify PTEN or P-AKT levels. Unexpectedly, while progesterone (P4) is assumed protective in uterine cancers, serum P4 was significantly higher in PTENKO females compared to WT, ARKO, and PTENARKO females consistent with more corpora lutea in PTENKO ovaries. Serum testosterone and ovarian estradiol were similar between all females. Hence, our results demonstrated AR inactivation mediated protection against PTENKO induced uterine pathology and suggests a potential role for antiandrogens in uterine cancer prevention and treatment.

Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis.

Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound.

Mixed pathology is more likely in black than white decedents with Alzheimer dementia.

To compare the burden of neuropathology in black and white participants with clinical Alzheimer disease (AD). Participants included 122 persons enrolled in the Rush Alzheimer's Disease Clinical Core, a prospective cohort study of AD. Forty-one black decedents were matched two-to-one to 81 white decedents according to age at death, sex, years of education, and cognition proximate to death. We examined common brain pathologies related to dementia (AD, Lewy body, and macroscopic and microinfarct pathology) and arteriolar sclerosis and atherosclerosis. We calculated the frequency of each dementia pathology both alone and in combination (mixed pathologies). Racial differences in the odds of a single pathology vs mixed pathologies, and in the odds of vessel disease and its severity, were examined using logistic regression analyses. AD pathology was confirmed in >93% of both black and white decedents with AD dementia. However, black decedents were less likely to have Alzheimer pathology as a single dementia pathology than white decedents (19.5% vs 42.0%), and were more likely to have AD mixed with an additional pathology (70.7% vs 50.6%), particularly Alzheimer pathology and Lewy bodies, and Alzheimer pathology, Lewy bodies, and infarcts. Black decedents also had more severe arteriolar sclerosis and atherosclerosis. Black decedents with AD dementia are more likely to have mixed brain pathologies compared with age-, sex-, education-, and cognition-matched white decedents with AD dementia.

Detection of Mild and Reversible Neurohistopathological Changes in the Brain of Juvenile (Preweaned) Beagle Dogs Treated with Vigabatrin for up to 91 Days.

Neurohistopathological changes in the brain were assessed in juvenile beagle dogs given vigabatrin at 30 or 100 mg/kg/day by oral gavage from postnatal day 22 (PND22) until 16 weeks of age (PND112), when brain myelination is considered to reach the adult stage in dogs. Separate subgroups were treated from PND22 to PND35 or PND36 to PND49 to assess early effects. In addition to extensive brain histopathology, there were assessments of toxicokinetics, clinical condition, body weight, organ weights, and macroscopic pathology. In animals treated for 14 days from PND22, minimal or slight vacuolation was seen in the neuropil of the septal nuclei, hippocampus, hypothalamus, thalamus, cerebellum, and globus pallidus at 100 mg/kg/day and minimal vacuolation in the thalamus, globus pallidus, and cerebellum at 30 mg/kg/day. In animals given 100 mg/kg/day for 91 days from PND22, minimal or slight vacuolation was observed only in the hippocampus, hypothalamus, and thalamus. No vigabatrin-related brain vacuolation was observed in animals given 30 or 100 mg/kg/day for 14 days from PND36. Clear evidence of recovery was observed after 14-day and 6-week off-dose periods that followed treatment from PND22 to PND35 or PND22 to PND112, respectively.

Cellular modelling in functional tissue engineering: review oriented for pelvic floor dysfunctions

This paper aims to review the current strategies for pelvic floor dysfunctions (PFDs). PFDs, such as stress urinary incontinence, foecal incontinence and vaginal prolapse affect the quality of life in women, involve high healthcare costs, and pose poor long-term success rates. As the problem progresses the cells in the pelvic tissues are impaired. The rheological relations between PFD and the damage of the tissues is not yet well established, bringing out clinical repair interventions, instead of knowing the root problem. As a consequence, the verification of damage mechanisms in the pelvic structures should be observed at cellular scales to correlate with the macroscopic phenomenological pathologies, namely, the changes in the mechanical properties and on the geometric configuration of the pelvic structures. Cells sense mechanical stimuli and respond biochemically via mechanotransduction mechanisms. Therefore, investigations on the cell dynamics must be performed, considering the physical conditions inside the bioreactors, to shed insight into the active behaviour of the cells during the treatment. These investigations should establish the conditions that push a cell to or keep a cell in a desired state during a regenerative treatment. This paper reviews the use of human adult stem cells to regenerate the defective muscles, ligaments and connective tissues in the pelvic floor, focusing on the role of the computational models as an assistive technology for these emergent tissue engineering treatments. First, the pelvic floor anatomy and physiology is related with the kinematic and mechanical behaviour of those structures at the tissue and cell scales. After, the relevance of the regenerative treatments is discussed and the requirements for their application are summarised. Later, the developments on computational models are exposed and the main guidelines for regeneration of the pelvic cavity tissues are proposed.

A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.