Immune Cell-Based Microrobots for Remote Magnetic Actuation, Antitumor Activity, and Medical Imaging.

Translating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage-based microrobots. This study presents living macrophage-based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor-killing state. The macrophage-based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft-tissue-mimicking phantoms and ex vivo conditions. Magnetic actuation and real-time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage-based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof-of-concept feasibility of integrating macrophage-based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications.

Pangolin-inspired untethered magnetic robot for on-demand biomedical heating applications.

Untethered magnetic miniature soft robots capable of accessing hard-to-reach regions can enable safe, disruptive, and minimally invasive medical procedures. However, the soft body limits the integration of non-magnetic external stimuli sources on the robot, thereby restricting the functionalities of such robots. One such functionality is localised heat generation, which requires solid metallic materials for increased efficiency. Yet, using these materials compromises the compliance and safety of using soft robots. To overcome these competing requirements, we propose a pangolin-inspired bi-layered soft robot design. We show that the reported design achieves heating > 70 °C at large distances > 5 cm within a short period of time <30 s, allowing users to realise on-demand localised heating in tandem with shape-morphing capabilities. We demonstrate advanced robotic functionalities, such as selective cargo release, in situ demagnetisation, hyperthermia and mitigation of bleeding, on tissue phantoms and ex vivo tissues.

Multifunctional 3D-Printed Pollen Grain-Inspired Hydrogel Microrobots for On-Demand Anchoring and Cargo Delivery.

While a majority of wireless microrobots have shown multi-responsiveness to implement complex biomedical functions, their functional executions are strongly dependent on the range of stimulus inputs, which curtails their functional diversity. Furthermore, their responsive functions are coupled to each other, which results in the overlap of the task operations. Here, a 3D-printed multifunctional microrobot inspired by pollen grains with three hydrogel components is demonstrated: iron platinum (FePt) nanoparticle-embedded pentaerythritol triacrylate (PETA), poly N-isopropylacrylamide (pNIPAM), and poly N-isopropylacrylamide acrylic acid (pNIPAM-AAc) structures. Each of these structures exhibits their respective targeted functions: responding to magnetic fields for torque-driven surface rolling and steering, exhibiting temperature responsiveness for on-demand surface attachment (anchoring), and pH-responsive cargo release. The versatile multifunctional pollen grain-inspired robots conceptualized here pave the way for various future medical microrobots to improve their projected performance and functional diversity.

Remotely Guided Immunobots Engaged in Anti-Tumorigenic Phenotypes for Targeted Cancer Immunotherapy.

Building medical microrobots from the body's own cells may circumvent the biocompatibility concern and hence presents more potential in clinical applications to improve the possibility of escaping from the host defense mechanism. More importantly, live cells can enable therapeutically relevant functions with significantly higher efficiency than synthetic systems. Here, live immune cell-derived microrobots from macrophages, i.e., immunobots, which can be remotely steered with externally applied magnetic fields and directed toward anti-tumorigenic (M1) phenotypes, are presented. Macrophages engulf the engineered magnetic decoy bacteria, composed of 0.5 µm diameter silica Janus particles with one side coated with anisotropic FePt magnetic nanofilm and the other side coated with bacterial lipopolysaccharide (LPS). This study demonstrates the torque-based surface rolling locomotion of the immunobots along assigned trajectories inside blood plasma, over a layer of endothelial cells, and under physiologically relevant flow rates. The immunobots secrete signature M1 cytokines, IL-12 p40, TNF-α, and IL-6, and M1 cell markers, CD80 and iNOS, via toll-like receptor 4 (TLR4)-mediated stimulation with bacterial LPS. The immunobots exhibit anticancer activity against urinary bladder cancer cells. This study further demonstrates such immunobots from freshly isolated primary bone marrow-derived macrophages since patient-derivable macrophages may have a strong clinical potential for future cell therapies in cancer.

Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery.

Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuli-responsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli-based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.

3D printed personalized magnetic micromachines from patient blood-derived biomaterials.

While recent wireless micromachines have shown increasing potential for medical use, their potential safety risks concerning biocompatibility need to be mitigated. They are typically constructed from materials that are not intrinsically compatible with physiological environments. Here, we propose a personalized approach by using patient blood­derivable biomaterials as the main construction fabric of wireless medical micromachines to alleviate safety risks from biocompatibility. We demonstrate 3D printed multiresponsive microswimmers and microrollers made from magnetic nanocomposites of blood plasma, serum albumin protein, and platelet lysate. These micromachines respond to time-variant magnetic fields for torque-driven steerable motion and exhibit multiple cycles of pH-responsive two-way shape memory behavior for controlled cargo delivery and release applications. Their proteinaceous fabrics enable enzymatic degradability with proteinases, thereby lowering risks of long-term toxicity. The personalized micromachine fabrication strategy we conceptualize here can affect various future medical robots and devices made of autologous biomaterials to improve biocompatibility and smart functionality.

Globalisation and Ocular Parasitic Infections: A Review of Recent Studies.

Ocular parasitic infections, which lead to significant morbidity and mortality in particular areas, have been shifting from endemic areas to other regions due to tourism, wars and migrations in recent years. This study aimed to review the parasitic factors related to the human eye and their geographical distribution, pathogenesis of the disease and the methods used in and studies conducted for its diagnosis. PubMed, MEDLINE and Google databases were researched and reviewed for relevant keywords in recent publications. Although such parasitic infections are rare in many parts of the world, they continue to be an important public health problem that affects human and animal health in places with poor health conditions. The distribution of ocular parasites and their spread to non-endemic areas are facilitated. The morbidity and mortality risks have been increasing due to the difficulties encountered by health personnel in the diagnosis of these parasitic infections. Defining them accurately and appropriately can save not only eyesight but also lives.

High-Yield Production of Biohybrid Microalgae for On-Demand Cargo Delivery.

Biohybrid microswimmers exploit the swimming and navigation of a motile microorganism to target and deliver cargo molecules in a wide range of biomedical applications. Medical biohybrid microswimmers suffer from low manufacturing yields, which would significantly limit their potential applications. In the present study, a biohybrid design strategy is reported, where a thin and soft uniform coating layer is noncovalently assembled around a motile microorganism. Chlamydomonas reinhardtii (a single-cell green alga) is used in the design as a biological model microorganism along with polymer-nanoparticle matrix as the synthetic component, reaching a manufacturing efficiency of ≈90%. Natural biopolymer chitosan is used as a binder to efficiently coat the cell wall of the microalgae with nanoparticles. The soft surface coating does not impair the viability and phototactic ability of the microalgae, and allows further engineering to accommodate biomedical cargo molecules. Furthermore, by conjugating the nanoparticles embedded in the thin coating with chemotherapeutic doxorubicin by a photocleavable linker, on-demand delivery of drugs to tumor cells is reported as a proof-of-concept biomedical demonstration. The high-throughput strategy can pave the way for the next-generation generation microrobotic swarms for future medical active cargo delivery tasks.

CADASIL with Atypical Clinical Symptoms, Magnetic Resonance Imaging, and Novel Mutations: Two Case Reports and a Review of the Literature.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy with adult onset caused by a missense mutation in the NOTCH3 gene in chromosome 19p13. It presents with autosomal dominant arteriopathy, subcortical infarctions, and leukoencephalopathy. Its common clinical presentations are seen as recurrent strokes, migraine or migraine-like headaches, progressive dementia, pseudobulbar paralysis, and psychiatric conditions. Two patients with CADASIL syndrome, whose diagnosis was made based on clinical course, age of onset, imaging findings, and genetic assays in the patients and family members, are presented here because of new familial polymorphisms. The first patient, with cerebellar and psychotic findings, had widespread non-confluent hyperintense lesions as well as moderate cerebellar atrophy in cranial magnetic resonance scanning. The other patient, with headache, dizziness, and forgetfulness, had gliotic lesions in both cerebral hemispheres. CADASIL gene studies revealed a new polymorphism in exon 33 in the first patient. In the other patient, the NOTCH3 gene was identified as a new variant of p.H243P (c.728A > C heterozygous). By reporting a family presenting with various clinical symptoms in the presence of new polymorphisms, we emphasize that CADASIL syndrome may present with various clinical courses and should be considered in differential diagnoses.

A novel method for PEGylation of chitosan nanoparticles through photopolymerization.

An ultrafast and convenient method for PEGylation of chitosan nanoparticles has been established through a photopolymerization reaction between the acrylate groups of PEG and methacrylated-chitosan nanoparticles. The nanoparticle characteristics under physiological pH conditions were optimized through altered PEG chain length, concentration and duration of UV exposure. The method developed here has potential for clinical translation of chitosan nanoparticles. It also allows for the scalable and fast synthesis of nanoparticles with colloidal stability.

Deep Insight into PEGylation of Bioadhesive Chitosan Nanoparticles: Sensitivity Study for the Key Parameters Through Artificial Neural Network Model.

Ionically cross-linked chitosan nanoparticles have great potential in nanomedicine due to their tunable properties and cationic nature. However, low solubility of chitosan severely limits their potential clinical translation. PEGylation is a well-known method to increase solubility of chitosan and chitosan nanoparticles in neutral media; however, effect of PEG chain length and chitosan/PEG ratio on particle size and zeta potential of nanoparticles are not known. This study presents a systematic analysis of the effect of PEG chain length and chitosan/PEG ratio on size and zeta potential of nanoparticles. We prepared PEGylated chitosan chains prior to the nanoparticle synthesis with different PEG chain lengths and chitosan/PEG ratios. To precisely estimate the influence of critical parameters on size and zeta potential of nanoparticles, we both developed an artificial neural network (ANN) model and performed experimental characterization using the three independent input variables: (i) PEG chain length, (ii) chitosan/PEG ratio, and (iii) pH of solution. We studied the influence of PEG chain lengths of 2, 5, and 10 kDa and three different chitosan/PEG ratios (25 mg chitosan to 4, 12, and 20 µmoles of PEG) for the synthesis of chitosan nanoparticles within the pH range of 6.0-7.4. Artificial neural networks is a modeling tool used in nanomedicine to optimize and estimate inherent properties of the system. Inherent properties of a nanoparticle system such as size and zeta potential can be estimated based on previous experiment results, thus, nanoparticles with desired properties can be obtained using an ANN. With the ANN model, we were able to predict the size and zeta potential of nanoparticles under different experimental conditions and further confirmed the cell-nanoparticle adhesion behavior through experiments. Nanoparticle groups that had higher zeta potentials promoted adhesion of HEK293-T cells to nanoparticle-coated surfaces in cell culture medium, which was predicted through ANN model prior to experiments. Overall, this study comprehensively presents the PEGylation of chitosan, synthesis of PEGylated chitosan nanoparticles, utilizes ANN model as a tool to predict important properties such as size and zeta potential, and further captures the adhesion behavior of cells on surfaces prepared with these engineered nanoparticles.

Three Pentatrichomonas hominis Cases Presenting with Gastrointestinal Symptoms.

We aimed to demonstrate that Pentatrichomonas hominis may also be an agent, although rare, in diarrheal episodes. Stool samples were first examined macroscopically and microscopically during routine parasitological examinations. Samples were then evaluated by Native-Lugol and formol-ethyl acetate centrifugation method. To exclude other pathogenic bacterial agents, a bacteriological culture method was applied. Samples were evaluated using a qualitative immunochromatographic test kit for rotavirus and adenovirus. We presented three cases of 77-year-old and 10-year-old male and 9-year-old female patients. Cases 1 and 2 were admitted to the hospital with complaints of diarrhea, abdominal pain, and weakness in July 2013. Leukocytes and active P. hominis trophozoites were detected. No bacterial and other parasitic and viral agents were found in their stool specimens. Oral metronidazole treatments were administered to the patients. In Case 3, P. hominis trophozoites were detected in the cellophane band in the plastic locked bag which could survive for 48 hduring a field survey in May 2012. Case 3 was contacted and advised to visit a pediatrician. P. hominis is a rare parasitic zoonosis, and we believe that it should not be ignored among diarrheal agents.

Improving science teachers' nature of science views through an innovative continuing professional development program.

BACKGROUND: This study describes how teachers' nature of science (NOS) views changed throughout an innovative Continuing Professional Development (CPD) program that provided sustained support throughout the process in a collaborative and reflective environment and activities that are consistent with the current curriculum and NOS tenets integrated within. Eighteen in-service science teachers enrolled in a yearlong nature of science, Continuing Professional Development (NOS-CPD) program. Data were collected by pre/post-interviews using the Views of Nature of Science-Form C (VNOS-C) questionnaire, and a post-interview using an open-ended questionnaire developed by researchers to uncover teacher reactions to the NOS-CPD program. RESULTS: The results indicated that the NOS-CPD program improved the teachers' NOS views more effectively than previously reported short-term teacher development programs, and thus, the findings should be useful for future studies in support of the professional development of teachers. CONCLUSIONS: The article concludes with practical advice for implementing NOS-focused, in-service teacher development programs.

Subtype distribution of Blastocystis spp. isolated from children in Eskisehir, Turkey.

Blastocystis spp. is the most common enteric protist found in human feces. The pathogenic role of Blastocystis remains controversial and it has been suggested that the symptomatology of Blastocystis is associated with its subtypes (ST). However, only few studies have investigated the relationship between the symptomatology and subtypes of Blastocystis in children. This study aimed to investigate the prevalence of Blastocystis in children aged 3 to 13years with or without gastrointestinal complaints and determine the distribution of the subtypes of Blastocystis. A total of 303 stool samples obtained from symptomatic (n=84) and asymptomatic (n=219) children were included in the study. The presence of Blastocystis was investigated using native-lugol examination, trichrome staining and real-time PCR method. Using the real-time PCR method, 115 samples were found positive for Blastocystis. Subtyping was successfully performed on 46 samples using sequenced-tagged site (STS) primers and PCR. The remaining 69 samples could not be subtyped. The most frequently detected subtype was ST3 (43.4%) followed by ST1 (26.1%), ST4 (10.9%) and ST2 (8.7%). The mixed subtypes were identified in five samples (10.9%) as; ST1+ST3 (n=3), ST1+ST2 (n=1) and ST2+ST3 (n=1). None of the samples had ST5, ST6 or ST7. No statistically significant difference was found between the symptomatic and asymptomatic groups in terms of the Blastocystis positivity and the distribution of subtypes (p>0.05). To our knowledge, this is the first study to investigate the subtype distribution of Blastocystis in children in Turkey and the results are in agreement with the related data available in Turkey.

[Comparison of direct microscopy, culture, ELISA and molecular methods for diagnosis of Entamoeba histolytica]. / Entamoeba histolytica'nin tanisinda direkt mikroskopi, kültür, ELISA ve moleküler yöntemlerin karsilastirilmasi

Amebiasis, a parasitic infection caused by Entamoeba histolytica, is one of the most common parasitic infections worldwide. Since it is still an important public health problem in developing countries, rapid differential diagnosis of amebiasis is crucial in terms of treatment. The most frequently used method for laboratory diagnosis is direct microscopy, however more reliable and specific methods are needed in order to differentiate the apathogenic Entamoeba dispar under the microscope. This study was conducted to compare the results of different methods namely, direct microscopy, culture, ELISA and PCR for the detection of E.histolytica in stool samples and to evaluate the performances of those methods. A total of 1049 stool samples collected from pediatric and adult patients who were admitted to hospital with diarrhea complaint between January 2011-March 2013, and randomly selected samples from primary school children, were included in the study. Direct microscopic examination was performed by native-lugol, physiological saline, modified formol-ethyl acetate sedimentation and trichrome staining methods. The stool samples were also inoculated into TYI-S-33 media for axenic cultivation of amoeba. The presence of amebic antigens in the samples were screened by a commercial ELISA kit (TechLab, E.histolytica II, USA). For the molecular diagnosis, a multiplex tandem real-time PCR (MT-PCR) kit (AusDiagnostics Pty Ltd, Australia) was used, after the extraction of DNAs with QIAamp DNA Stool Mini Kit (Qiagen, USA). A total of 354 samples which could be evaluated by all of the methods, were included in the study. Of the 354 stool samples, 84 (23.7%) were found E.histolytica/E.dispar positive by direct microscopy, 61 (17.2%) by trichrome staining, 46 (12.9%) by culture, 31 (8.7%) by ELISA and 9 (2.5%) by MT-PCR. Of direct microscopy positive samples 54.7% (46/84) were also positive with trichrome staining, 39.3% (33/84) with culture, 15.5% (13/84) with ELISA and 7.1% (6/84) with MT-PCR methods. On the other hand, of the nine MT-PCR positive samples, six were positive with direct microscopy, four with trichrome staining and culture, and one with ELISA. It was remarkable that only one (0.3%) sample yielded positive results with all of the diagnostic methods used. When MT-PCR was considered as the reference method, the sensitivity and specificity values of direct microscopy, trichrome staining, culture and ELISA methods were estimated as; 66.7% and 77.4%, 44.4% and 83.5%, 44.4% and 87.8%, 11.1% and 91.3%, respectively. In conclusion, if the circumstances allow, the use of all methods in combination and evaluation together with the clinical symptoms seems to be the best approaches for the laboratory diagnosis of patients with amebiasis.

[Case of polyparasitism with long-term abdominal pain in a patient]. / Uzun Süreli Karin Agrisi Sikayeti Olan Hastada Poliparazitizm Olgusu.

It is known that infections caused by intestinal protozoa and helminths affect over 3.5 million people worldwide. In this case report, a patient with complaints of stomach ache for a long time who received thermal treatment is presented. During this thermal treatment, diarrhoea occurred and multiparasitism was diagnosed with two helminths; pseudoparasitism and multiprotozoa, simultaneously. Stool samples were collected from the patient on three consecutive days and one day after the treatment. All of the samples were prepared with formalin-ether sedimentation techniques after macroscopic and direct microscopic investigation. Cellophane-tape method for Enterobius vermicularis and Taenia spp. and Erlich-Ziehl-Neelsen staining method for coccidian parasites were used. At least four preparations were performed for each sample and serum physiologic, lugol' solution and trichrome stain were used for microscopic investigations.The motile segment she brought was investigated microscopically with Indian ink and identified as Taenia saginata. Under direct microscopy, Blastocystis hominis, Endolimax nana and Fasciola hepatica were seen. By formalin-ether sedimentation techniques, Ascaris lumbricoides, Fasciola hepatica, Blastocystis hominis, Endolimax nana and Entamoeba coli were identified. In recent years, intestinal parasitism is rarely seen in our city; therefore, multiparasitism in an adult and immunocompetent patient is interesting.

[Comparison of individual differences in the direct microscopic examination in the diagnosis of intestinal parasites]. / Bagirsak Parazitlerinin Tanisinda Direkt Mikroskobik Incelemedeki Bireysel Farkliliklarin Karsilastirilmasi

OBJECTIVE: The aim is to emphasise the importance for intestinal parasites' diagnosis by direct microscopic examination and the discrepancies among results from different microscopists. METHODS: Stool specimens were obtained from 225 children with diarrhoea after the macroscopic examination, prepared by formalineether sedimentation methods and included in microscopically examination by three different independent investigators (parasitologist, microbiologist, research assistant). Furthermore, specimens were stained with the modified Ehrlich Ziehl Neelsen method and evaluated for Cryptosporidium and Cyclospora. RESULTS: A total 161 specimens were evaluated as negative by all investigators. The number of specimens containing parasites detected by at least one investigator was 64; Cryptosporidium parvum 30, Blastocytis hominis 16, Endolimax nana 5, Giardia intestinalis 4, Dientamoeba fragilis 3, Ascaris lumbricoides 3, Entamoeba histolytica/dispar 2, Cyclospora cayetanensis 1. The concordance among investigators was observed for 21 (33%) specimens; when specimens were evaluated for the presence of leukocytes and/or parasites, concordance was detected for 58 (91%) of the 64 specimens. In particular, significant differences were observed for the species level identification. CONCLUSION: Different results can be obtained by microscopic examination according to the experience and educational level of microscopists. Therefore, we think that these tests should be performed by persons who have sufficient education and experience, if possible, combined with at least two different methods.

Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection.

Although many Blastocystis infections remain asymptomatic, recent data suggest it also causes frequent symptoms. Therapy should be limited to patients with persistent symptoms and a complete workup for alternative etiologies. The goal of this study was to compare the natural evolution (no treatment) to the efficacy of Saccharomyces boulardii (S. boulardii) or metronidazole for the duration of diarrhea and the duration of colonization in children with gastrointestinal symptoms and positive stool examination for Blastocystis hominis. This randomized single-blinded clinical trial included children presenting with gastrointestinal symptoms (abdominal pain, diarrhea, nausea-vomiting, flatulence) more than 2 weeks and confirmed B. hominis by stool examination (B. hominis cysts in the stool with microscopic examination of the fresh stool). The primary end points were clinical evaluation and result of microscopic stool examination at day 15. Secondary end points were the same end points at day 30. Randomization was performed by alternating inclusion: group A, S. boulardii (250 mg twice a day, Reflor®) during 10 days; group B, metronidazole (30 mg/kg twice daily) for 10 days; group C, no treatment. At day 15 and 30 after inclusion, the patients were re-evaluated, and stool samples were examined microscopically. On day 15, children that were still symptomatic and/or were still B. hominis-infected in group C were treated with metronidazole for 10 days. There was no statistically significant difference between the three study groups for age, gender, and the presence of diarrhea and abdominal pain. On day 15, clinical cure was observed in 77.7% in group A (n, 18); in 66.6% in group B (n, 15); and 40% in group C (n:15) (p < 0.031, between groups A and C). Disappearance of the cysts from the stools on day 15 was 80% in group B, 72.2% in group A, and 26.6% in group C (p = 0.011, between group B and group C; p = 0.013, between group A and group C). At the end of the first month after inclusion, clinical cure rate was 94.4% in group A and 73.3% in group B (p = 0.11). Parasitological cure rate for B. hominis was very comparable between both groups (94.4% vs. 93.3%, p = 0.43). Metronidazole or S. boulardii has potential beneficial effects in B. hominis infection (symptoms, presence of parasites). These findings challenge the actual guidelines.

[The struggle against malaria in the Ottoman Empire during World War I and the legal regulations made to this end]. / Birinci dünya savasi sirasinda osmanli devleti'nde sitma mücadelesi ve bu amaçla yapilan yasal düzenlemeler.

One of the most important disadvantages of war environmental is infectious diseases. The Ottoman Empire combated infectious diseases in addition to the war because of Balkan wars and afterwards first world war. Because of increasing migrations to Anatolia after Balkan wars spread some epidemic diseases, such as cholera, typhoid fever, plaque, dysentery, syphilis. With the start of the First World War, malaria began to spread within civilian population as well as the military. The population fell from power because of illness and therefore could not process the land tax failed to pay taxes. Founded in 1914 with the fight against epidemic diseases was initiated by the Sihhiye ministry. Quinine was formed as tablets which was imported from Germany by legal regulation and was distributed to the public by Ziraat Bank. However, malaria epidemic could not be prevented because of long war years, lack of population, insufficiency of the preventive methods and lack of quinine, and about three quarters of the population caught malaria and in four years 412.000 soldiers had malaria and 20.000 of them died despite of measures.

[Cyclospora cayetanensis and Cryptosporidium parvum coinfection in a pregnant woman with prolonged diarrhoea]. / Uzamis ishalli hamile bir kadinda Cyclospora cayetanensis ve Cryptosporidium parvum koenfeksiyonu.

Cyclospora cayetanensis which is a recently described pathogen, is associated with prolonged diarrheae and history of travelling to tropical regions and intake of suspicious food and water. Cryptosporidium parvum is another pathogen that causes severe diarrhea defined initially in especially AIDS patients since 1980's. Cases of cyclosporiasis are frequently missed, since it is difficult to detect the parasite in human fecal samples, despite an increasing amount of data regarding this parasite. To identify both of these coccidian protozoa, faeces should be examined by modified acid-fast stain. Co-incidence of C. cayetanensis and C. parvum is seen rarely in Turkey. In this case report, C. cayetanensis and C. parvum found in a 28 years old pregnant women living in continental climate and without a history of travel, were presented. The patient had prolonged diarrhea and investigation of the feces by modified acid-fast and carbol fuchsin stains revealed C. cayetanensis and C. parvum. The immunoglobulin and lymphocyte subgroup testing done for the evaluation of the immune status of the patient, were all within normal limits. Following treatment with trimethoprim-sulfamethoxazole for 15 days, the oocyst number in feces has decreased. However, hepatic vein thrombosis and liver failure have developed in the postnatal period and she was diagnosed as Budd-Chiari syndrome. It was concluded that when the effect of pregnancy on immunity was taken into account, C. cayetonensis and C. parvum should be considered in cases of prolonged diarrhoeae in pregnant women.