The Lifeways of Early Kantharodai, Sri Lanka

In the 1st millennium BCE Sri Lanka was central to the wide-spanning trading networks in the Western Indian Ocean region. Population agglomerations grew on the coast and further inland, where Anuradhapura emerged as the major central place. Parallel agglomerations formed in the south in Tissamaharama and in the north on Jaffna Peninsula in Kantharodai. The site of Kantharodai on the northern tip of Sri Lanka is the largest known early historic mound site on the Jaffna Peninsula, thought to represent the ancient centre of the region. The Early Historic occupation of Kantharodai began ca. 400-100 BCE. In our study we focus on the older historic occupation phase at Kantharodai, represented by a rich midden deposit of domestic refuse that offer insights into the environmental conditions faced by early occupants of the site and their modes of subsistence. We provide a glimpse into the subsistence strategies of the earliest settled population in Kantharodai who augmented a diet based on domesticated livestock through multiple wild species from forests, swamps, mangroves and marine habitats. Based on the faunal evidence from early Kantharodai, this complex socio-economic structure appears to have been in operation, confirming proposed models of mixed economies in operation in the Early Historic period of the region

Predicting low-risk prostate cancer from transperineal saturation biopsies

Introduction: To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods: Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA \u3c10 ng/mL, Gleason score \u3c8 PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5mm total max core length PC + ≤3mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume \u3c2.5mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume \u3c0.7 mL). Results: 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC. Conclusions: Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies. prostate cancer screening (PSA), testing practices, United Kingdom, Australia, qualitative stud

Prevalence and sequelae of penile lichen sclerosus in males presenting for circumcision in regional Australia: a multicentre retrospective cohort study

Background: Lichen sclerosus (LS) in men commonly involves the external genitalia, with up to 20% of these patients developing urethral stricture disease, and a small group developing malignant transformation to penile squamous cell carcinoma (SCC). The objective of this study was to determine the prevalence of LS and its sequelae in males presenting for circumcision. Methods: A multicentre retrospective cohort study was conducted at 8 hospitals within 3 Australian regional centres. We identified males who underwent circumcision between January 2004 and November 2018 and obtained histological and clinical data. Histopathological confirmation of LS was the primary outcome. Development of urethral stricture disease and penile cancer were secondary outcomes. Results: Six hundred and eleven patients underwent circumcision, of which 313 (51.2%) had a specimen sent for histology. Of these, 199 (63.6%) had confirmed LS where the median age at diagnosis was 65 years [interquartile range (IQR), 40–77]. Even if the remainder of unsent specimens were free of LS, the prevalence would still be 32.6%. Amongst the patients with LS, 44 (22.1%) developed urethral strictures, 1 penile SCC (0.5%), and 1 penile intraepithelial neoplasia (0.5%). Conclusions: The prevalence of LS in patients undergoing circumcision where the foreskin was sent for histopathological review was 63.6%. In those with LS, the prevalence of urethral stricture disease was 22.1%

A Process Similar to Autophagy is Associated with Cytocidal Chloroquine Resistance in Plasmodium Falciparum

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ LD50. Candidate genes in these loci are consistent with a role for autophagy in CQR(CC), leading us to directly examine the autophagy pathway in intraerythrocytic CQR parasites. Indirect immunofluorescence of RBC infected with synchronized CQS vs CQR trophozoite stage parasites reveals differences in the distribution of the autophagy marker protein PfATG8 coinciding with CQR(CC). Taken together, the data show that an unusual autophagy-like process is either activated or inhibited for intraerythrocytic trophozoite parasites at LD50 doses (but not IC50 doses) of CQ, that the pathway is altered in CQR P. falciparum, and that it may contribute along with mutations in PfCRT to confer the CQR(CC) phenotype

A Process Similar to Autophagy is Associated with Cytocidal Chloroquine Resistance in Plasmodium Falciparum

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ LD50. Candidate genes in these loci are consistent with a role for autophagy in CQR(CC), leading us to directly examine the autophagy pathway in intraerythrocytic CQR parasites. Indirect immunofluorescence of RBC infected with synchronized CQS vs CQR trophozoite stage parasites reveals differences in the distribution of the autophagy marker protein PfATG8 coinciding with CQR(CC). Taken together, the data show that an unusual autophagy-like process is either activated or inhibited for intraerythrocytic trophozoite parasites at LD50 doses (but not IC50 doses) of CQ, that the pathway is altered in CQR P. falciparum, and that it may contribute along with mutations in PfCRT to confer the CQR(CC) phenotype

An unusually large myofibroblastoma in a male breast: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myofibroblastoma of the breast is a rare benign stromal tumour seen predominantly in men. The gross appearance is that of a well-circumscribed nodule, characteristically small, seldom exceeding 3 cm. We present a case of an unusually large myofibroblastoma, which mimicked a malignant breast tumour.</p> <p>Case presentation</p> <p>A 65-year-old man presented with a rapid enlargement of the right breast over 6 weeks. Examination revealed a firm 15 cm hemispherical lump occupying the whole of the right breast with peau d'orange appearance of the overlying skin and distortion of the nipple. The clinical and radiological features suggested the possibility of sarcoma of the breast. However, a guided Tru-Cut biopsy was inconclusive. A mastectomy was performed to remove the tumour, which weighed more than 2 kg. Histopathology and immunocytochemistry revealed a mixed classical and collagenised type of myofibroblastoma. The patient is well with no evidence of recurrence 5 years after the mastectomy.</p> <p>Conclusion</p> <p>This unexpected presentation of an unusually large myofibroblastoma in a male breast is the largest reported to date. Myofibroblastomas can mimic malignant neoplasms and the clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.</p

Short term effects on liver and renal functions following chemotherapy treatment for breast cancer patients in oncology clinic, university hospital Kotelawala Defence University in Sri Lanka

Background: Breast cancer tops the global cancer incidence rates, having the highest rate of death among women. The primary objective of this study was to assess the impact of standard chemotherapy treatment dose adjusted for the Sri Lankan population, on hepatic and kidney function of breast cancer patients. Methods: The study conducted a cross-sectional, retrospective and prospective analysis of 75 breast cancer patients who received doxorubicin, cyclophosphamide, and paclitaxel chemotherapy regimen with normal liver and renal function at baseline at UHKDU oncology clinic. The study population had a mean age and BMI of 54.04±11.33 years and 26.7±3.89, respectively. Prior to starting the 16-cycle chemotherapy treatment, mean serum SGOT, SGPT, Creatinine, and eGFR values were 27.57 U/l, 31.32 U/l, 0.71 mg/dl, and 99.07 ml/minute/1.73 m2 respectively. Results: During the treatment, there was a statistically significant increase in the mean values of SGOT and SGPT (p&lt;0.05), whereas there was no significant variation in the mean values of creatinine and eGFR (p&gt;0.05) compared to the baseline results. The study identified a significant positive correlation in SGOT (r=0.793) and SGPT (r=0.872) values, while there was a noteworthy negative correlation (r=-0.757) between eGFR and chemotherapy cycle. Furthermore, there was a positive significant correlation between serum creatinine levels and chemotherapy cycle (r=0.579). Conclusions: The dosed adjusted chemotherapy regimen had a significant impact on hepatic function but had no statistically significant impact on renal function among the study population. Further research is recommended to evaluate the long-term effects of standard chemotherapy treatment on liver and kidney functions

Evaluation of Luffa (Luffa acutangula (L.) Roxb) varieties under low country intermediate zone of Sri Lanka

Luffa (Luffa acutangulu) is a popular low country vegetable in Sri Lanka and it is one of the mosthighly utilized vegetable species in the fanning systems of dry and intermediate zones. The existingLuffa varieties in Sri Lanka, recommended by the Department of Agriculture, and the introducedhybrids are vulnerable to pests and diseases and the cost for pest control mainly accounts for thehigher production cost of Luffa. Makandura Selection (MK) is a Luffa variety selected from farmerfields and it shows tolerance to fruit fly (Bactrocera cucurbitae (Coquillettj), which is the mostserious pest causing high level of economic losses. Therefore, an experiment was conducted at theRegional Agricultural Research and Development Centre, Makandura, to evaluate the performanceof Makandura Selection along with the two Department of Agricu Iture recommended Luffa varieties,Asiri and LA 33. The experiment was laid out in a randomized complete block design with fourreplicates. Evaluation was done based on reproductive, yield and fruit quality parameters. Though thevariety LA 33 recorded the significantly highest yield (9.08 t/ha), the higher fruit length (35.02 ern),higher fruit weight (280.5 g) and high fruit firmness (4.38 kg) were not desirable in the context ofconsumer preference. The variety Asiri recorded a significantly lower yield (7.05 t ha') and thelowest fruit firmness (3.89 kg) wh ich are not preferred by the farmers. The variety MakanduraSelection showed moderate yields (8.98 t ha') and better performance in fruit quality attributes suchas lower fru it length (21.7 ern), lower fru it weight (207.2 g) and moderate firmness (4.25 kg). Therefore,the fruit fly tolerant ability, along with these positive fruit characteristics makes Makandura Selectiona suitable variety to introduce to the Luffa growers in Sri Lanka after further testing

Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens

Modular assembly of proteins on nanoparticles

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond