Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis.

Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline.

The RAS proto-oncogene Harvey rat sarcoma viral oncogene homolog (HRAS) encodes a small GTPase that transduces signals from cell surface receptors to intracellular effectors to control cellular behavior. Although somatic HRAS mutations have been described in many cancers, germline mutations cause Costello syndrome (CS), a congenital disorder associated with predisposition to malignancy. Based on the epidemiology of CS and the occurrence of HRAS mutations in spermatocytic seminoma, we proposed that activating HRAS mutations become enriched in sperm through a process akin to tumorigenesis, termed selfish spermatogonial selection. To test this hypothesis, we quantified the levels, in blood and sperm samples, of HRAS mutations at the p.G12 codon and compared the results to changes at the p.A11 codon, at which activating mutations do not occur. The data strongly support the role of selection in determining HRAS mutation levels in sperm, and hence the occurrence of CS, but we also found differences from the mutation pattern in tumorigenesis. First, the relative prevalence of mutations in sperm correlates weakly with their in vitro activating properties and occurrence in cancers. Second, specific tandem base substitutions (predominantly GC>TT/AA) occur in sperm but not in cancers; genomewide analysis showed that this same mutation is also overrepresented in constitutional pathogenic and polymorphic variants, suggesting a heightened vulnerability to these mutations in the germline. We developed a statistical model to show how both intrinsic mutation rate and selfish selection contribute to the mutational burden borne by the paternal germline.

F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation.

Modulation of the sonic hedgehog (SHH) pathway is a crucial factor in cerebellar morphogenesis. Stimulation of granule neuron progenitor (GNP) proliferation is a central function of SHH signalling, but how this is controlled locally is not understood. We show that two sequentially expressed members of the contactin (CNTN) family of adhesion molecules, TAG1 and F3, act antagonistically to control SHH-induced proliferation: F3 suppresses SHH-induced GNP proliferation and induces differentiation, whereas TAG1 antagonises F3. Production of GNPs in TAG1-null mice is delayed and reduced. F3 and TAG1 colocalise on GNPs with the related L1-like adhesion molecule NrCAM, and F3 fails to suppress the SHH-induced proliferation of NrCAM-deficient GNPs. We show that F3 and SHH both primarily affect a group of intermediate GNPs (IPs), which, though actively dividing, also express molecules associated with differentiation, including ß-tubulin III (TuJ1) and TAG1. In vivo, intermediate progenitors form a discrete layer in the middle of the external germinal layer (mEGL), while F3 becomes expressed on the axons of postmitotic granule neurons as they leave the inner EGL (iEGL). We propose, therefore, that F3 acts as a localised signal in the iEGL that induces SHH-stimulated cells in the overlying mEGL to exit cell cycle and differentiate. By contrast, expression of TAG1 on GNPs antagonises this signal in the mEGL, preventing premature differentiation and sustaining GNP expansion in a paracrine fashion. Together, these findings indicate that CNTN and L1-like proteins play a significant role in modulating SHH-induced neuronal precursor proliferation.

Protective effect of sucrose esters from cape gooseberry (Physalis peruviana L.) in TNBS-induced colitis.

Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.

Preparation and application of stimuli-responsive PET TeMs: RAFT graft block copolymerisation of styrene and acrylic acid for the separation of water-oil emulsions.

Stimuli-responsive membranes play an important role in the fields of biomedicine, food and chemical industries, and environmental applications, including separation of water-oil emulsions. In this study, we present a method to fabricate pH-sensitive membranes using UV-initiated RAFT graft copolymerization of styrene (ST) and acrylic acid (AA) on poly(ethylene terephthalate) (PET) track-etched membranes (TeMs). The optimization of polymerization conditions led to successful grafting of polystyrene (PS) and poly(acrylic acid) (PAA) onto PET TeMs, resulting in membranes with stable hydrophobicity and pH change responsiveness. The membranes show a contact angle of 65° in basic environments (pH 9) and 97° in acidic environments (pH 2). The membranes were characterized by atomic force microscopy (AFM), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), thermogravimetric analyses (TGA), Fourier transform infrared spectroscopy (FTIR), contact angle (CA) methods. The PET TeMs-g-PS-g-PAA exhibited good performance in separating water-oil emulsions with a high efficiency of more than 90% and flux for direct chloroform-water 2500 L m-2 h-1 and reverse emulsions of benzene-water 1700 L m-2 h-1. This method of preparing stimuli-responsive membranes with controlled wettability and responsiveness to environmental pH provides versatility in their use in separating two types of emulsions: direct and reverse.

Facial Nerve Preserving Subtotal Excision for Large Vestibular Schwannoma: An Institution-Based Functional Outcome Study.

BACKGROUND: The ideal goal of treatment for medium to large vestibular schwannoma is complete tumor removal with preservation of all cranial nerves. However, despite the advancements in microsurgery and intraoperative monitoring, the risk of facial nerve dysfunction following total resection varies between 31% and 57%. Currently, the goal of treatment for large tumors is shifting from total excision to facial nerve preservation. OBJECTIVE: To evaluate the facial nerve outcome in patients who underwent subtotal excision with or without subsequent gamma knife radiosurgery for large vestibular schwannomas in our institute. METHODS AND MATERIAL: All patients who underwent primary surgery for large vestibular schwannomas between January 2012 and December 2016 were analyzed retrospectively. Cases where total excision was not done and a residue was left behind to prevent facial nerve injury during surgery were included in the study. RESULTS: A total of 52 patients who met the inclusion criteria were analyzed. At final follow-up, 70% of patients had good facial nerve function (H-B grade 1 and 2). In patients with normal facial nerve function preoperatively, 81% (25/31) of them had good facial nerve outcomes (H-B grade 1 and 2), whereas in patients with preexisting facial nerve deficits, nearly 62% (13/21) of them either maintained or had improvement in their facial nerve grades. CONCLUSION: Good facial nerve outcomes and tumor control rate is obtained by subtotal excision of VS followed by upfront or delayed GKRS; however, there is a need for long-term follow-up to detect recurrences in these slow-growing tumors.

The fibroblast growth factor receptor 2 p.Ala172Phe mutation in Pfeiffer syndrome--history repeating itself.

Pfeiffer syndrome is an autosomal dominant condition classically combining craniosynostosis with digital anomalies of the hands and feet. The majority of cases are caused by heterozygous mutations in the third immunoglobulin-like domain (IgIII) of FGFR2, whilst a small number of cases can be attributed to mutations outside this region of the protein. A mild form of Pfeiffer syndrome can rarely be caused by a specific mutation in FGFR1. We report on the clinical and genetic findings in a three generation British family with Pfeiffer syndrome caused by a heterozygous missense mutation, p.Ala172Phe, located in the IgII domain of FGFR2. This is the first reported case of this particular mutation since Pfeiffer's index case, originally described in a German family in 1964, on which basis the syndrome was eponymously named. Genetic analysis demonstrated the two families to be unrelated. Similarities in phenotypes between the two families are discussed. Independent genetic origins, but phenotypic similarities in the two families add to the evidence supporting the theory of selfish spermatogonial selective advantage for this rare gain-of-function FGFR2 mutation.

Tools for identifying and prioritizing evidence-based obesity prevention strategies, Colorado.

Colorado's adult obesity rate has more than doubled since 1995, prompting its Department of Public Health and Environment to list obesity as its top prevention priority. To initiate comprehensive and effective action, the department used a well-known evidence-based public health framework developed by Brownson and others. This article describes the tools and process developed to conduct 2 of the 7 stages in this framework that challenge public health organizations: reviewing the literature and prioritizing effective strategies from that literature. Forty-five department staff participated in an intensive literature review training to identify physical activity and nutrition strategies that effectively address obesity and worked with external stakeholders to prioritize strategies for the state. Divided into 8 multidisciplinary teams organized by the setting where public health could exert leverage, they scanned the scientific literature to identify potential strategies to implement. These teams were trained to use standardized tools to critique findings, systematically abstract key information, and classify the evidence level for each of 58 identified strategies. Next, departmental subject matter experts and representatives from local public health and nonprofit health agencies selected and applied prioritization criteria to rank the 58 strategies. A team charter, group facilitation tools, and 2 web-based surveys were used in the prioritization stage. This process offered the staff a shared experience to gain hands-on practice completing literature reviews and selecting evidence-based strategies, thereby enhancing Colorado's obesity prevention efforts and improving public health capacity. Practitioners can use these tools and methodology to replicate this process for other health priorities.

Stimuli-Responsive Track-Etched Membranes for Separation of Water-Oil Emulsions.

In this work, we have developed a method for the preparation of pH-responsive track-etched membranes (TeMs) based on poly(ethylene terephthalate) (PET) with pore diameters of 2.0 ± 0.1 µm of cylindrical shape by RAFT block copolymerization of styrene (ST) and 4-vinylpyridine (4-VP) to be used in the separation of water-oil emulsions. The influence of the monomer concentration (1-4 vol%), the molar ratio of RAFT agent: initiator (1:2-1:100) and the grafting time (30-120 min) on the contact angle (CA) was studied. The optimal conditions for ST and 4-VP grafting were found. The obtained membranes showed pH-responsive properties: at pH 7-9, the membrane was hydrophobic with a CA of 95°; at pH 2, the CA decreased to 52°, which was due to the protonated grafted layer of poly-4-vinylpyridine (P4VP), which had an isoelectric point of pI = 3.2. The obtained membranes with controlled hydrophobic-hydrophilic properties were tested by separating the direct and reverse "oil-water" emulsions. The stability of the hydrophobic membrane was studied for 8 cycles. The degree of purification was in the range of 95-100%.

Intraoperative assessment of STA-MCA bypass patency using near-infrared indocyanine green video-angiography: a preliminary study.

BACKGROUND: Bypass patency is critical for patients undergoing superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. Near-infrared indocyanine green video-angiography (ICGA) is an excellent method to assess vessels during cerebrovascular surgery. OBJECTIVE: The aim of the present study is to analyze the effectiveness of ICGA in patients undergoing STA-MCA anastomosis for moyamoya disease. MATERIALS AND METHODS: This study was a retrospective review of case records and operation records of patients who underwent STA-MCA bypass for moyamoya disease at our institute. Concordance of ICGA with intraoperative micro-Doppler and postoperative angiography, whenever available, was assessed. RESULTS: In all, 22 STA-MCA anastomoses were performed in 13 patients. ICGA was used to assess patency in 14 surgeries (10 patients). No patient required revision of anastomosis following ICGA. Postoperative angiography was done in five anastomoses (three patients) at three months follow-up and correlated well with ICGA findings in all cases. CONCLUSION: ICGA is an effective technique to assess bypass patency during cerebrovascular surgery. Routine use of ICGA in cerebral bypass surgery improves graft patency and minimizes complications due to graft occlusion.

Prediction of Durability of Thermal Insulating Epoxy Coatings with Regard to Climatic Ageing.

It is generally accepted that the color and performance characteristics of liquid thermal insulation coatings are affected by the combined effect of various climatic factors such as solar radiation, temperature fluctuations, moisture, precipitation and others. This work presents the results of a scientific study of the full-scale exposure of coatings with regard to climatic ageing. Methods have been carried out, such as: spectrophotometry and direct scanning; determining adhesion, determining the adhesion strength of facing and protective coatings; and thermal conductivity and thermal resistance. As the results of the research work have shown, only in situ climatic tests, accompanied by the obligatory recording of the aggressive factors affecting the coating, make it possible to assess changes in the properties of epoxy coatings in full-scale conditions and, consequently, their climatic resistance by the methods of spectrophotometry and direct scanning. The ageing of polymer composites is known to be accompanied by a change not only in elasticity but also in color. Of the epoxy coatings tested, Etal-45M showed the greatest color variation during the in situ climate test. The most decorative resistant coatings are obtained using epoxy resin ED-20 + modified epoxy resin Etal-1440N.

Graft Polymerization of Stearyl Methacrylate on PET Track-Etched Membranes for Oil-Water Separation.

In this article, results of PET track-etched membranes (PET TeMs) hydrophobized by photo-induced graft polymerization of stearyl methacrylate (SM) inside the pores were presented. The effects of monomer concentration, time of irradiation and the nature of the solvent on the degree of grafting and membrane morphology were investigated. The PET TeMs with pore diameters ranging from 350 nm (pore density of 1 × 108 pore/cm2) to 3.05 µm (pore density of 1 × 106 pore/cm2) were hydrophobized and tested for oil-water separation by using hexadecane-water and chloroform-water emulsions. Studies have shown high separation performance for membranes (up to 1100 mL/m2·s) with large pore diameters while achieving a high degree of purification.

Preparation of Hydrophobic PET Track-Etched Membranes for Separation of Oil-Water Emulsion.

The paper describes the separation of an oil-water emulsion by filtration using poly(ethylene terephthalate) track-etched membranes (PET TeMs) with regular pore geometry and narrow pore size distribution. PET TeMs were modified with trichloro(octyl)silane to increase their hydrophobic properties. Conditions for the modification of PET TeMs with trichloro(octyl)silane were investigated. The results of changes in the pore diameters and the contact angle depend on the concentration of trichloro(octyl)silane and the soaking time are presented. The obtained samples were characterized by FTIR, AFM, SEM-EDX and gas-permeability test. Chloroform-water and cetane-water emulsions have been used as a test liquid for oil-water separation.

A variant in the sonic hedgehog regulatory sequence (ZRS) is associated with triphalangeal thumb and deregulates expression in the developing limb.

A locus for triphalangeal thumb, variably associated with pre-axial polydactyly, was previously identified in the zone of polarizing activity regulatory sequence (ZRS), a long range limb-specific enhancer of the Sonic Hedgehog (SHH) gene at human chromosome 7q36.3. Here, we demonstrate that a 295T>C variant in the human ZRS, previously thought to represent a neutral polymorphism, acts as a dominant allele with reduced penetrance. We found this variant in three independently ascertained probands from southern England with triphalangeal thumb, demonstrated significant linkage of the phenotype to the variant (LOD = 4.1), and identified a shared microsatellite haplotype around the ZRS, suggesting that the probands share a common ancestor. An individual homozygous for the 295C allele presented with isolated bilateral triphalangeal thumb resembling the heterozygous phenotype, suggesting that the variant is largely dominant to the wild-type allele. As a functional test of the pathogenicity of the 295C allele, we utilized a mutated ZRS construct to demonstrate that it can drive ectopic anterior expression of a reporter gene in the developing mouse forelimb. We conclude that the 295T>C variant is in fact pathogenic and, in southern England, appears to be the most common cause of triphalangeal thumb. Depending on the dispersal of the founding mutation, it may play a wider role in the aetiology of this disorder.

Treatment Experience and Repeat Pregnancy Impact the Effectiveness of Non-Nucleoside Reverse Transcription Inhibitor-Highly Active Antiretroviral Therapy for the Prevention of Mother to Child Transmission of Human Immunodeficiency Virus.

Non-nucleoside reverse transcription inhibitor (NNRTI)-containing antiretroviral therapy (ART) for the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) has led to dramatic reductions in perinatal HIV infection in resource-constrained settings. Nonetheless, PMTCT programs are complicated by repeat pregnancies, in which long-term or repeat exposures to PMTCT regimens over time may lead to the acquisition of HIV drug resistance mutations, and consequent treatment failure. In this study, we retrospectively assessed the effectiveness of the NNRTI-based PMTCT protocol from 2008 to 2010 in The Bahamas National HIV/AIDS Program. We show that women who had been in repeat pregnancies and those who were already prescribed ART at conception were at increased risk of virologic failure, relative to treatment-inexperienced women and primigravida, respectively (AOR 3.1, 95% CI: 1.3-7.1, p = .008 and AOR 5.0, 95% CI: 1.8-14.1, p = .002). In addition, women undergoing treatment at conception were more likely to possess HIVDR mutations relative to treatment-naive women (AOR 447.1, 95% CI: 17.9-11,173.5, p = .001). Therefore, individual treatment history is a key metric determining the effectiveness of current and future PMTCT interventions. The implications of this to PMTCT programmatic success in light of the most recent WHO guidelines are discussed.

Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2 In Vitro Virus Neutralization in Convalescent Plasma.

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.

Rare mutations of FGFR2 causing apert syndrome: identification of the first partial gene deletion, and an Alu element insertion from a new subfamily.

Apert syndrome (AS) is a severe disorder, characterized by craniosynostosis and complex syndactyly of the hands and feet. Two heterozygous gain-of-function substitutions (Ser252Trp and Pro253Arg) in exon IIIa of fibroblast growth factor receptor 2 (FGFR2) are responsible for >98% of cases. Here we describe two novel mutations in FGFR2 in the two patients in whom a mutation had not previously been found in our cohort of 227 AS cases. The first is a 1.93-kb deletion, removing exon IIIc and substantial portions of the flanking introns. This is the first large FGFR2 deletion described in any individual with craniosynostosis. The other mutation is a 5' truncated Alu insertion into exon IIIc. This is the third Alu insertion identified in AS; all have occurred within an interval of only 104 bp, representing an enrichment of over a million-fold compared to the background genomic rate. We show that the inserted Alu element belongs to a small subfamily, not previously known to be mobile, which we term Alu Yk13. Both the deletion and insertion are likely to act by a similar gain-of-function mechanism in which disruption of exon IIIc leads to illegitimate mesenchymal expression of an FGFR2 spliceform containing the alternatively spliced exon IIIb. All the AS-associated Alu insertions have arisen in the paternal germline; we propose that their enrichment in FGFR2 is driven by positive selection of the mutant spermatogonial progenitors, a mechanism analogous to that explaining why the canonical AS nucleotide substitutions also reach exceptionally high levels in sperm.

Performance of and preference for oral rapid HIV testing in The Bahamas.

Initiatives to increase access to quality rapid HIV diagnostics have had relative success in the Caribbean in recent years, including use of oral rapid HIV testing. However, to date, there has not been any investigation into the performance or acceptability of oral fluids HIV testing in the region. In this cross-sectional study in The Bahamas, 252 persons of unknown serostatus were tested side-by-side with two oral rapid test brands, and the results were compared with the national fingerprick algorithm. In addition, an exit survey was administered to 234 study participants to assess user test preference. The most frequent survey response was to have no test preference (47.8%), but of those who expressed a test preference, most preferred oral (34.4%) versus fingerprick (17.8%) method. Both OraQuick and AWARE were 100% concordant with the gold standard. Therefore, our results show that oral fluids rapid testing is preferred over fingerprick testing by a subset of the potential target population and performs well in a population of undiagnosed persons attending screening clinic in The Bahamas.

Central nervous system cladosporiosis: an account of ten culture-proven cases.

BACKGROUND: Central nervous system (CNS) cladosporiosis is a rare infection caused by Cladophialophora bantiana. It has varied presentation and poor outcome. Most of the available data in the literature are reviews of individual case reports. OBJECTIVE: To describe the clinical, radiological and mycological features of 10 cases of C. bantiana managed at a single tertiary center. To analyze the various treatment options, factors associated with outcome and to review the relevant literature. MATERIALS AND METHODS: This is a retrospective study of 10 patients with CNS cladosporiosis managed at National Institute of Mental Health and Neurosciences from 1979 to 2006. It is a descriptive study. The case records were reviewed for clinical presentation, radiological features, management and outcome. Only those patients in whom the fungus could be isolated on culture were included in the study. RESULTS: The age of the patients ranged from three to 42 years. Nine patients presented with features of space-occupying lesion and one patient with chronic meningitis. There were no specific clinical or radiological features. None of patients had impaired immune status. This infection presented as two pathomorphological forms - diffuse meningoencephalitis and focal abscesses. Burr hole tapping and excision are the surgical options. Both patients with burr hole tapping required excision of abscess subsequently. Two out of seven patients with abscess expired compared to all three patients with diffuse meningoencephalitis who expired. Recurrences occurred in four of the five patients following excision of the abscess. Combination antifungal treatment had better result than monotherapy. The outcome was poor with survival of only 50%. CONCLUSIONS: Thorough microbiological examination is required to diagnose CNS infection caused by C. bantiana. The outcome is better in patients with abscess. Excision of the abscess followed by combination antifungal therapy results in better outcome. Close follow-up is required due to high risk of recurrence.