Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial Candida glabrata isolates.

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

Cribra orbitalia is a vascular phenomenon unrelated to marrow hyperplasia or anemia: Paradigm shift for cribra orbitalia.

The orbital phenomenon, cribra orbitalia, has long been a source of controversy, especially with regard to its nature, derivation, and relationship to anemia. Therefore, the external surfaces of orbital roofs were systematically examined microscopically in human skulls from historical collections. Superior orbital surfaces of 278 individual crania within the Hamann-Todd collection were assessed at various magnifications using epi-illumination microscopy to identify the presence of cribra orbitalia and characterize its nature. Also, 12 additional individuals with diagnosed anemia in the Hamann-Todd collection were evaluated. Orbital roof alterations, present in one-third of examined crania, had two discrete appearances: Vascular grooves (45%) and application of new bone in a vascular branching pattern on the orbit surface (55%). Porosity of the orbit was not observed. Evaluation of the orbits of 12 individuals with diagnosed anemia revealed one with a single deep defect, suggesting a space-occupying phenomenon, but no evidence of bone accretion, vascular grooves, or porosity. Cribra orbitalia has often been lumped indiscriminately as an indicator of organismal stress, rather than identified as a indicating a specific etiology. Neither that perspective nor porosity are supported by high resolution examination of orbital roof changes. Recognition of the blood vessel imprint pattern falsifies previous speculations and provides a new paradigm. The actual character of cribra orbitalia is documented and new hypotheses generated. While population prevalence of cribra orbitalia seems excessive for explanation on the basis of these hypotheses, the imprints are clearly vascular in origin.

Full Facial Allotransplantation Including the Temporomandibular Joints: A Radiologic and Anatomical Cadaveric Study.

BACKGROUND: Facial allotransplantation including the temporomandibular joints may improve the functional outcomes in face transplant candidates who have lost or damaged this joint. METHODS: Linear and angular measurements were taken in 100 dry skulls and mandibles and in 100 three-dimensionally-reconstructed facial computed tomographic scans to determine the variability of the temporomandibular joint, glenoid fossa, and mandible. A vascular study was performed in six fresh cadaveric heads, followed by harvest of the face allograft in three heads. Next, four heads were used for mock transplantation (two donors and two recipients). The full facial allograft included four different segments: a Le Fort III, a mandibular tooth-bearing, and two condyle and temporomandibular joint-bearing segments. Statistical analysis was performed using SAS software. RESULTS: In only one-third of the skulls, the condylar shape was symmetric between right and left sides. There was a wide variability in the condylar coronal (range, 14.3 to 23.62 mm) and sagittal dimensions (range, 5.64 to 10.96 mm), medial intercondylar distance (range, 66.55 to 89.91 mm), and intercondylar angles (range, 85.27 to 166.94 degrees). This high variability persisted after stratification by sex, ethnicity, and age. The temporomandibular joint was harvested based on the branches of the superficial temporal and maxillary arteries. The design of the allograft allowed fixation of the two condyle and temporomandibular joint-bearing segments to the recipient skull base, preserving the articular disk-condyle-fossa relationship, and differences were adjusted at the bilateral sagittal split osteotomy sites. CONCLUSION: Procurement and transplantation of a temporomandibular joint-containing total face allograft is technically feasible in a cadaveric model.

Comparison of Orbital Volume in Young Versus Senescent Human Skulls.

PURPOSE: To compare bony orbital volumes in young skulls with those of older skulls to elucidate aging-associated changes of the orbit. METHODS: One hundred Caucasian male skulls from the Hamann-Todd collection of the Cleveland Museum of Natural History were studied. There were 50 young skulls (age range, 19-33 years) and 50 senescent skulls (age range, 79-96 years). Volcanic sand was used to fill each orbit in an identical fashion and weighed as a proxy for volume. Digital calipers were used to perform linear measurements of the orbit. The relationship between orbit measures and skull size was assessed using Pearson's correlations and 95% CI, and statistical models to compare age groups adjusted for skull size. RESULTS: The volume of the orbits (P < 0.001), the horizontal diameter of the orbit (P = 0.015), and the orbital depth (P < 0.001) were significantly larger in the senescent group of skulls after adjusting for skull surface area. No significant differences were found in the vertical diameters of the orbit between the 2 groups. Skull size did not statistically differ between the age groups. CONCLUSIONS: Increases in the depth and horizontal dimensions of the orbit lead to increasing bony orbital volume with increasing age. These changes in size and shape of the orbit with age may contribute to phenotypic changes of aging and may affect disease processes and management.

A dermatological questionnaire for general practitioners in England with a focus on melanoma; misdiagnosis in black patients compared to white patients.

BACKGROUND: Malignant melanoma presents a significant health burden in the UK in terms of mortality and financial cost. This aggressive and often fatal disease is under-diagnosed among patients with darker skin tones (type 5 and 6) such as Afro-Caribbean patients. A lack of both patient and practitioner awareness leads to a later diagnosis in patients with black compared to white skin. There is currently a paucity of literature looking at the diagnosis rates of melanoma between patients of different ethnicities in the UK and the reasons behind these differences. OBJECTIVE: The primary aim was to obtain data on the diagnosis rate of melanoma in the primary care setting, with particular attention to white vs. black skin types. METHODS: An online questionnaire was sent to 2975 general practitioner (GP) practices in England and 287 responses were received. The questionnaire contained 20 high-quality picture questions of differing common skin conditions. The participants were asked to choose their diagnosis from 20 potential diagnoses. Only 4/20 questions were melanomas, two on white and two on black skin. No accompanying histories were provided. RESULTS: The mean score for the questionnaire was 11.6/20 (58%) with a range from 5% to 100%. Of the two black skin melanoma pictures, 177/287 (62%) and 90/287 (31%) responses were incorrectly identified, compared to 37/287 (13%) and 19/287 (7%) in the white skin melanoma pictures. CONCLUSION: The questionnaire results show a clear increased misdiagnosis of melanoma in black patients in primary care vs. white. The results suggest that vigilance is needed when diagnosing possible melanoma in black patients and better quality melanoma teaching is required in GP training concentrating on pigmented skin. This pilot study should encourage more research into ethnic skin inequalities in the UK.

Predictability of Optic Foramen Location From a Ray Through the Ethmoidal Foramina.

PURPOSE: To determine how accurately a ray through the anterior and posterior ethmoidal foramina predicts the location of the optic foramen. METHODS: Dried, well-preserved, complete human skulls without bony defects belonging to the Hamann-Todd osteological collection of the Cleveland Museum of Natural History were examined. Photography was performed and a ray was drawn on orbit photographs extending through the center of the anterior and posterior ethmoidal foramina toward the optic canal. The location of the ray at the anterior aspect of the optic canal was recorded. RESULTS: Sixty-six total orbits were examined from 36 skulls with 6 skulls with only unilateral data. Thirty-eight orbits were of African descent and 28 were of European descent with an average age 45.25 years (range = 19-89 years). The anterior-posterior ethmoidal foramen ray extended superior (12/66), through (53/66), and inferior (1/66) to the optic canal. Of those rays passing through the optic canal, 32/53 (60%) passed through the upper one-third, 19/53 (36%) passed through the middle one-third, and 2/53 (4%) passed through the lower one-third of the optic canal. CONCLUSIONS: The anterior-posterior ethmoidal foramen ray highly predicts the superior aspect of the optic canal. This information can guide medial orbital wall surgery.

Classification of pelvic ring fractures in skeletonized human remains.

Pelvic ring fractures are associated with high rates of mortality and thus can provide key information about circumstances surrounding death. These injuries can be particularly informative in skeletonized remains, yet difficult to diagnose and interpret. This study adapted a clinical system of classifying pelvic ring fractures according to their resultant degree of pelvic stability for application to gross human skeletal remains. The modified Tile criteria were applied to the skeletal remains of 22 individuals from the Cleveland Museum of Natural History and Universidad Nacional Autónoma de México that displayed evidence of pelvic injury. Because these categories are tied directly to clinical assessments concerning the severity and treatment of injuries, this approach can aid in the identification of manner and cause of death, as well as interpretations of possible mechanisms of injury, such as those typical in car-to-pedestrian and motor vehicle accidents.

Visualization of an alphaherpesvirus membrane protein that is essential for anterograde axonal spread of infection in neurons.

UNLABELLED: Pseudorabies virus (PRV), an alphaherpesvirus with a broad host range, replicates and spreads in chains of synaptically connected neurons. The PRV protein Us9 is a small membrane protein that is highly conserved among alphaherpesviruses and is essential for anterograde axonal spread in neurons. Specifically, the Us9 protein is required for the sorting of newly assembled PRV particles into axons. However, the molecular details underlying the function of Us9 are poorly understood. Here we constructed PRV strains that express functional green fluorescent protein (GFP)-Us9 fusion proteins in order to visualize axonal transport of viral particles in infected rat superior cervical ganglion neurons. We show that GFP-Us9-labeled structures are transported exclusively in the anterograde direction within axons. Additionally, the vast majority of anterograde-directed capsids (labeled with VP26-monomeric red fluorescent protein) and a viral membrane protein (labeled with glycoprotein M fused to mCherry) are cotransported with GFP-Us9 in the anterograde direction. In contrast, during infection with PRV strains that express nonfunctional mutant GFP-Us9 proteins, cotransport of mutant GFP-Us9 with capsids in axons is abolished. These findings show that axonal sorting of progeny viral particles is dependent upon the association of viral structures with membranes that contain functional Us9 proteins. This association is required for anterograde spread of infection in neurons. IMPORTANCE: Alphaherpesviruses, such as pseudorabies virus (PRV), are parasites of the mammalian nervous system. These viruses spread over long distances in chains of synaptically connected neurons. PRV encodes several proteins that mediate directed virion transport and spread of infection. Us9 is a highly conserved viral membrane protein that is essential for anterograde neuronal spread of infection. In the absence of Us9, newly replicated viral particles are assembled in the cell body but are not sorted into or transported within axons. Here, we constructed and characterized novel PRV strains that express functional green fluorescent protein (GFP)-Us9 fusion proteins in order to visualize its localization in living neurons during infection. This enabled us to better understand the function of Us9 in facilitating the spread of infection. We show that all viral particles moving in the anterograde direction are labeled with GFP-Us9, suggesting that the presence of Us9 determines the capacity for directed transport within axons.

Comparison of the pseudorabies virus Us9 protein with homologs from other veterinary and human alphaherpesviruses.

Pseudorabies virus (PRV) Us9 is a small, tail-anchored (TA) membrane protein that is essential for axonal sorting of viral structural proteins and is highly conserved among other members of the alphaherpesvirus subfamily. We cloned the Us9 homologs from two human pathogens, varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1), as well as two veterinary pathogens, equine herpesvirus type 1 (EHV-1) and bovine herpesvirus type 1 (BHV-1), and fused them to enhanced green fluorescent protein to examine their subcellular localization and membrane topology. Akin to PRV Us9, all of the Us9 homologs localized to the trans-Golgi network and had a type II membrane topology (typical of TA proteins). Furthermore, we examined whether any of the Us9 homologs could compensate for the loss of PRV Us9 in anterograde, neuron-to-cell spread of infection in a compartmented chamber system. EHV-1 and BHV-1 Us9 were able to fully compensate for the loss of PRV Us9, whereas VZV and HSV-1 Us9 proteins were unable to functionally replace PRV Us9 when they were expressed in a PRV background.

Repair of the UL21 locus in pseudorabies virus Bartha enhances the kinetics of retrograde, transneuronal infection in vitro and in vivo.

The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the U(L)21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha U(L)21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.

Fusion of enhanced green fluorescent protein to the pseudorabies virus axonal sorting protein Us9 blocks anterograde spread of infection in mammalian neurons.

Pseudorabies virus encodes a membrane protein (Us9) that is essential for the axonal sorting of virus particles within neurons and anterograde spread in the mammalian nervous system. Enhanced green fluorescent protein (GFP)-tagged Us9 mimicked the trafficking properties of the wild-type protein in nonneuronal cells. We constructed a pseudorabies virus strain that expressed Us9-GFP and tested its spread capabilities in the rat visual system and in primary neuronal cultures. We report that Us9-EGFP does not promote anterograde spread of infection and may disrupt packing of viral membrane proteins in lipid rafts, an essential step for Us9-mediated axonal sorting.

Pseudorabies virus Us9 directs axonal sorting of viral capsids.

Pseudorabies virus (PRV) mutants lacking the Us9 gene cannot spread from presynaptic to postsynaptic neurons in the rat visual system, although retrograde spread remains unaffected. We sought to recapitulate these findings in vitro using the isolator chamber system developed in our lab for analysis of the transneuronal spread of infection. The wild-type PRV Becker strain spreads efficiently to postsynaptic neurons in vitro, whereas the Us9-null strain does not. As determined by indirect immunofluorescence, the axons of Us9-null infected neurons do not contain the glycoproteins gB and gE, suggesting that their axonal sorting is dependent on Us9. Importantly, we failed to detect viral capsids in the axons of Us9-null infected neurons. We confirmed this observation by using three different techniques: by direct fluorescence of green fluorescent protein-tagged capsids; by transmission electron microscopy; and by live-cell imaging in cultured, sympathetic neurons. This finding has broad impact on two competing models for how virus particles are trafficked inside axons during anterograde transport and redefines a role for Us9 in viral sorting and transport.

Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma.

Using whole genome expression microarray technology to discover clinically relevant biomarkers for pilocytic astrocytoma (PA), the authors identified matrilin-2 as a unique mRNA overexpressed in PA. Matrilin-2 protein expression was similarly elevated in the majority of sporadic PA, but in only one neurofibromatosis 1-associated PA with an unusually aggressive clinical phenotype. These results suggest that matrilin-2 may be a specific and clinically useful biomarker for discriminating between indolent and clinically aggressive PA.

Button osteoma: its etiology and pathophysiology.

The present study investigates a circumscribed bony overgrowth on the cranial vault, known as button osteoma (BtO) and referred to here as button lesion (BtL). We discuss its anthropological implications. Data on its histology, location, and population distribution (by age, race, and gender) are provided. Microscopically, BtL is composed of well-organized dense lamellated bone which is poorly vascularized and with very few osteocytes. It forms a dome-shaped roof over an underlying diploeized area which includes the ectocranial table. The frequency of BtL is similar in modern (37.6%) and archaeological (41.1%) populations, in blacks, whites, males, and females, and correlates with age. It is rare in nonhuman primates. Fifty-five percent of the human skulls studied by us had BtL only on the parietal, 23.6% on the frontal, and 3.6% on the occipital bones. Fifteen percent had BtL on both the frontal and parietal bones. No lateral preference was found. Most skulls with BtL (64.1%) had only one lesion, 20.4% had two BtL, and 15.4% demonstrated multiple BtL. The average number of button osteomas on an affected skull was 1.97. The frequency of large osteomas (0.5-1.0 cm) was similar in young and old age groups. The demographic characteristics of BtL, mainly its high frequency among ancient and modern populations, its independence of sex and race, its scarcity in other primates, and the fact that its macro- and microstruture are indicative of an hamartoma (and not an osteoma or exostosis) suggest an evolutionary background to the phenomenon.

Serpens endocrania symmetrica (SES): a new term and a possible clue for identifying intrathoracic disease in skeletal populations.

This paper describes a phenomenon in the endocranial plate, which we have termed "serpens endocrania symmetrica" (SES), and discusses its value as a diagnostic tool. The affected discolored bone area exhibits disruption of the endocranial surface, lending it a maze-like appearance. Histological sections demonstrate that the process is limited to the most superficial portion of the endocranium, with no diploic and ectocranial involvement (sinus areas excepted). Adult skulls (n = 1,884) from the Hamann-Todd collection (HTH), housed at the Cleveland Museum of Natural History, were utilized for the present study. SES was recognized in 32 of the 1,884 skulls studied (1.7%). The frequency of SES among individuals reported to have died from tuberculosis (TB) was 4.4%. The rate of SES in the non-TB sample was only 0.53%. The locations were as follows: limited to sinus area, 28.1%; calvarium (excluding the sinuses), 46.9%; sinus + calvarium, 25.0%. SES was bilateral in 90.9% of cases. Twenty-five of the 32 individuals (78.1%) with SES in the HTH collection had tuberculosis specifically listed as the cause of death. Six of the other 7 individuals had infections other than TB. In 29 of the 32 individuals with SES, infection involved structures within the thorax. As SES was also associated with another osteological phenomenon known to represent pulmonary disease, i.e., hypertrophic osteoarthropathy (HOA; 68.0% of SES individuals also had HOA), SES may be of diagnostic value in paleopathology for the recognition of intrathoracic disease, and perhaps tuberculosis.

Pathogenesis of virus-induced immune-mediated demyelination.

Theiler's murine encephalomyelitis virus-induced demyelinating disease has been extensively studied as an attractive infectious model for human multiple sclerosis. Virus-specific inflammatory Th1 cell responses followed by autoimmune responses to myelin antigens play a crucial role in the pathogenic processes leading to demyelination. Antibody and cytotoxic T cells (CTL) responses to virus appears to be primarily protective from demyelinating disease. Although the role of Th1 and CTL responses in the induction of demyelinating disease is controversial, assessment of cytokines produced locally in the central nervous system (CNS) during the course of disease and the effects of altered inflammatory cytokine levels strongly support the importance of Th1 responses in this virus-induced demyelinating disease. Induction of various chemokines and cytokines in different glial and antigen presenting cells upon viral infection appears to be an important initiation mechanism for inflammatory Th1 responses in the CNS. Coupled with the initial inflammatory responses, viral persistence in the CNS may be a critical factor for sustaining inflammatory responses and consequent immune-mediated demyelinating disease.

Evaluation of the SprayGel adhesion barrier in the rat cecum abrasion and rabbit uterine horn adhesion models.

OBJECTIVE: To evaluate the efficacy of a new adhesion barrier in the prevention of postoperative adhesion formation. DESIGN: A double-blind controlled study of the efficacy of SprayGel in reducing postoperative adhesion formation in two animal models. SETTING: Animal care facility of a contract testing laboratory. ANIMAL(S): Sixteen Sprague-Dawley male rats were randomly allocated into two groups in the cecum abrasion model. Twenty New Zealand white female rabbits were randomly allocated into two groups in the uterine horn abrasion model. INTERVENTION(S): In the rat model, the cecum was abraded with gauze and the abdominal wall was abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. In the rabbit model, uterine horns were abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. MAIN OUTCOME MEASURE(S): Postoperative adhesion formation. RESULT(S): In the rat model, SprayGel was found to significantly reduce the incidence of adhesions, which formed in 7 of 8 control rats compared with 1 of 8 treated rats. In the rabbit model, SprayGel was found to significantly reduce both the extent and severity of adhesions. CONCLUSION(S): Application of SprayGel in two animal models reduced formation of postoperative adhesions. Further investigation in large animal and clinical settings is warranted.

In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams.

This study investigated the in vitro degradation of porous poly(DL-lactic-co-glycolic acid) (PLGA) foams during a 20-week period in pH 7.4 phosphate-buffered saline (PBS) at 37 degrees C and their in vivo degradation following implantation in rat mesentery for up to 8 weeks. Three types of PLGA 85 : 15 and three types of 50 : 50 foams were fabricated using a solvent-casting, particulate-leaching technique. The two types had initial salt weight fraction of 80 and 90%, and a salt particle size of 106-150 microm, while the third type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.82, 0.89, and 0.85 for PLGA 85 : 15, and 0.73, 0.87, and 0.84 for PLGA 50 : 50 foams, respectively. The corresponding median pore diameters were 30, 50, and 17 microm for PLGA 85: 15, and 19, 17, and 17 microm for PLGA 50 : 50. The in vitro and in vivo degradation kinetics of PLGA 85: 15 foams were independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. The in vitro foam half-lives based on the weight average molecular weight were 11.1 +/- 1.8 (80%, 106-150 microm), 12.0 +/- 2.0 (90%, 106-150 microm), and 11.6 +/- 1.3 (90%, 0-53 microm) weeks, similar to the corresponding values of 9.4 +/- 2.2, 14.3 +/- 1.5, and 13.7 +/- 3.3 weeks for in vivo degradation. In contrast, all PLGA 50 : 50 foams exhibited significant change in foam weight, water absorption, and pore distribution after 6-8 weeks of incubation with PBS. The in vitro foam half-lives were 3.3 +/- 0.3 (80%, 106-150 microm), 3.0 +/- 0.3 (90%, 106-150 microm), and 3.2 +/- 0.1 (90%, 0-53 microm) weeks, and the corresponding in vivo half-lives were 1.9 micro 0.1, 2.2 +/- 0.2, and 2.4 +/- 0.2 weeks. The significantly shorter half-lives of PLGA 50: 50 compared to 85: 15 foams indicated their faster degradation both in vitro and in vivo. In addition, PLGA 50: 50 foams exhibited significantly faster degradation in vivo as compared to in vitro conditions due to an autocatalytic effect of the accumulated acidic degradation products in the medium surrounding the implants. These results suggest that the polymer composition and environmental conditions have significant effects on the degradation rate of porous PLGA foams.

In vitro degradation of porous poly(L-lactic acid) foams.

This study investigated the in vitro degradation of porous poly(L-lactic acid) (PLLA) foams during a 46-week period in pH 7.4 phosphate-buffered saline at 37 degrees C. Four types of PLLA foams were fabricated using a solvent-casting, particulate-leaching technique. The three types had initial salt weight fraction of 70, 80, and 90%, and a salt particle size of 106-150 microm, while the fourth type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.67, 0.79, 0.91, and 0.84, respectively. The corresponding median pore diameters were 33, 52, 91, and 34 microm. The macroscopic degradation of PLLA foams was independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. However, decrease in melting temperature and slight increase in crystallinity were observed at the end of degradation. The foam half-lives based on the weight average molecular weight were 11.6+/-0.7 (70%, 106-150 microm), 15.8+/-1.2 (80%, 106-150 microm), 21.5+/-1.5 (90%, 106-150 microm), and 43.0+/-2.7 (90%, 0-53 microm) weeks. The thicker pore walls of foams prepared with 70 or 80% salt weight fraction as compared to those with 90% salt weight fraction contributed to an autocatalytic effect resulting in faster foam degradation. Also, the increased pore surface/volume ratio of foams prepared with salt in the range 0-53 microm enhanced the release of degradation products thus diminishing the autocatalytic effect and resulting in slower foam degradation compared to those with salt in the range 106-150 microm. Formation and release of crystalline PLLA particulates occurred for foams fabricated with 90% salt weight fraction at early stages of degradation. These results suggest that the degradation rate of porous foams can be engineered by varying the pore wall thickness and pore surface/volume ratio.