Prediction of Shigellosis outcomes in Israel using machine learning classifiers.

Shigellosis causes significant morbidity and mortality in developing and developed countries, mostly among infants and young children. The World Health Organization estimates that more than one million people die from Shigellosis every year. In order to evaluate trends in Shigellosis in Israel in the years 2002-2015, we analysed national notifiable disease reporting data. Shigella sonnei was the most commonly identified Shigella species in Israel. Hospitalisation rates due to Shigella flexenri were higher in comparison with other Shigella species. Shigella morbidity was higher among infants and young children (age 0-5 years old). Incidence of Shigella species differed among various ethnic groups, with significantly high rates of S. flexenri among Muslims, in comparison with Jews, Druze and Christians. In order to improve the current Shigellosis clinical diagnosis, we developed machine learning algorithms to predict the Shigella species and whether a patient will be hospitalised or not, based on available demographic and clinical data. The algorithms' performances yielded an accuracy of 93.2% (Shigella species) and 94.9% (hospitalisation) and may consequently improve the diagnosis and treatment of the disease.

Evaluating the peptide structure prediction capabilities of a purely ab-initio method.

DEEPSAM is a relatively new global optimization algorithm aimed to predict the structure of bio-molecules from sequence, without any additional preliminary assumption. It is an evolutionary algorithm whose mutation operators are built by hybridizing the diffusion equation method, molecular dynamics simulated annealing, and a quasi-Newton local minimization method. The goal of this study was to evaluate the structure prediction capabilities of DEEPSAM by running it upon NMR structures of linear peptides (10-20 residues). The results indicate that DEEPSAM successfully predicted the conformations of these peptides, using modest computing resources.

Early enteral feeding and nosocomial sepsis in very low birthweight infants.

BACKGROUND: The interrelations between early enteral feeding, necrotising enterocolitis (NEC), and nosocomial sepsis (NS) remain unclear. OBJECTIVE: To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight (VLBW< 1500 g) infants. METHODS: Data were collected on the pattern of enteral feeding and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995-2001. Enteral feeding was compared between infants with and without NS and/or NEC. RESULTS: The study sample included 385 infants. Of these, 163 (42%) developed NS and 35 (9%) developed NEC. Enteral feeding was started at a significantly earlier mean (SD) age in infants who did not develop nosocomial sepsis (2.8 (2.6) v 4.8 (3.7) days, p = 0.0001). Enteral feeding was introduced at the same age in babies who did or did not develop NEC (3.1 (2) v 3.7 (3) days, p = 0.28). Over the study period, the mean annual age at the start of enteral feeding fell consistently, and this correlated with the mean annual incidence of NS (r(2) = 0.891, p = 0.007). Multiple logistic regression analysis showed age at start of enteral feeding, respiratory distress syndrome, and birth weight to be the most significant predictors of risk of NS (p = 0.0005, p = 0.024, p = 0.011). CONCLUSIONS: Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC in VLBW infants. These findings support the use of early enteral feeding in this high risk population, but this needs to be confirmed in a large randomised controlled trial.

High-dose liposomal amphotericin B in the therapy of systemic candidiasis in neonates.

High-dose (5-7 mg/kg/day) liposomal amphotericin B was evaluated prospectively during the period 1995-2001 in 41 episodes of systemic candidiasis occurring in 37 neonates (36 of the 37 were premature infants with very low birth weights). Median age at the onset of systemic candidiasis was 17 days. Candida spp. were isolated from blood in all patients and from urine, skin abscesses and peritoneal fluid in 6, 5 and 1 neonates, respectively. Candidiasis was due to Candida parapsilosis in 17 cases, Candida albicans in 15 cases, Candida tropicalis in 5 cases, Candida guilliermondii in 2 cases, Candida glabrata in 2 cases and an unidentified Candida sp. in 1 case. Twenty-eight, five and eight infants received 7, 6-6.5 and 5 mg/kg/day, respectively. Median duration of therapy was 18 days; median cumulative dose was 94 mg/kg. Fungal eradication was achieved in 39 of 41 (95%) episodes; median duration of therapy until fungal eradication was 8.7+/-4.5 days. Fungal eradication was achieved after 10.9+/-4.8 days in patients who had received previous antifungal therapy compared to 8.2+/-4.3 days in those treated with liposomal amphotericin B as first-line therapy. One patient died due to systemic candidiasis on day 12 of therapy. High-dose liposomal amphotericin B was effective and safe in the treatment of neonatal candidiasis. Fungal eradication was more rapid in patients treated early with high doses and in patients who received high-dose liposomal amphotericin B as first-line therapy.

Liposomal amphotericin B (AmBisome) in the treatment of neonatal candidiasis in very low birth weight infants.

UNLABELLED: AmBisome (2.5-7 mg/kg/day as a continuous 1 h infusion) was evaluated prospectively from September 1994 to January 1998 in 24 very low birth weight infants (mean birth weight 847+/-244 g, mean gestational age 26 weeks) with systemic candidiasis. Mean age at onset of candidemia was 17 days. One patient had two episodes of candidiasis. Thirteen infants failed previous antifungal therapy with amphotericin B (with or without 5-flucytosine). Candida spp. were isolated from the blood in all 25 episodes and from skin abscesses and urine in four infants each, respectively. There were 13 isolates of Candida albicans, ten of Candida parapsilosis, two of Candida tropicalis and one of Candida glabrata. One infant had a mixed infection with C. albicans and C. parapsilosis. The mean duration of therapy was 21 days; the cumulative AmBisome dose was 94 mg/kg. Fungal eradication was achieved in 92% of the episodes; mean duration of AmBisome therapy until achieving eradication was 9 days. Twenty (83%) infants were considered clinically cured at the end of treatment. No major adverse effects were recorded; one infant developed increased bilirubin and hepatic transaminases levels during therapy. Four (17%) infants died; in two of them (8%) the cause of death was directly attributed to systemic candidiasis. CONCLUSION: AmBisome represents an effective, safe and convenient antifungal agent in the therapy of systemic fungal infections in very low birth weight infants.

The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis.

The effects of recombinant granulocyte-colony stimulating factor (rhG-CSF) in neonatal neutropenia with presumed sepsis, which has a poor prognosis, were investigated. The study involved 14 neonates with presumed sepsis and neutropenia. Findings were compared with those from 24 historical controls. rhG-CSF (5 micrograms/ kg/day i.v. for 5 days) was administered immediately following diagnosis. Complete blood counts were obtained before and 24, 48, 72, 96 and 120 h after initiation of treatment. Neutrophil storage pool (NSP) was assessed (in 4 patients) before and after treatment. Statistical analysis was performed using one way analysis of variance. Treatment led to an increase in absolute neutrophil count (ANC) levels in 13/14 patients. At the end of treatment, the mean ANC was higher than that of controls (P = 0.007). There was a marked increase in the NSP of between 32% and 65% (P = 0.005). There were two clinical failures, one of whom was considered to have died from his underlying condition. There were no reports of clinical or haematological toxicity during treatment or follow up.

Sepsis at a neonatal intensive care unit: a four-year retrospective study (1989-1992).

During the 4-year period 1989-1992, 18,227 neonates were born at Kaplan Hospital and 614 (3.4%) were admitted to the neonatal intensive care unit. During this period, 120 episodes (6.6/1000 live births) of neonatal sepsis were recorded in 109 neonates (6/1000 live births). The incidence of early-onset sepsis was 19/109 (17%). The main pathogens of early-onset sepsis were S. agalactiae (42%) and E. coli (32%). Seven of the 8 S. agalactiae cases were recorded during 1989-1990. The main pathogens of late-onset sepsis were Klebsiella spp. (31%), coagulase-negative staphylococci (18%) and Candida spp (16%). There were 11 cases (10%) of meningitis, 5 due to Klebsiella spp. The overall fatality rate due to sepsis was 14% (0.8/1000 live births) with an early-onset sepsis death rate of 37%. The mortality from S. agalactiae sepsis was 63%. The main trends recorded during the period of the study were 1) the emergence of S. agalactiae as the main pathogen of early-onset sepsis, followed by a sharp decrease in its incidence during the last part of the study, 2) the emergence of extremely virulent, multi-antibiotic-resistant Klebsiella organisms, and 3) the persistent high incidence of Candida sepsis.

An outbreak of antibiotic multiresistant Klebsiella at the Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot, Israel, November 1991 to April 1992.

From November 1991 through April 1992, 8 infants developed systemic infections due to antibiotic multiple resistant Klebsiellaa (MRK). All were premature and 6 of the 8 weighed less than 1100 g; 7 of the 8 had received previous antibiotic therapy. Five infections occurred during the first week of life. MRK were isolated from blood (8 cases), tracheal secretions (TS-6), stool (3), and CSF (1). All Klebsiella blood isolates were resistant to ampicillin, mezlocillin, and cefotaxime, 7 of 8 to ceftazidime and amikacin, and 4 of 7 to aztreonam; all isolates were sensitive to quinolones and imipenem. Four infants died. In all 4 of the isolates, they were sensitive only to quinolones and imipenem, and the empiric therapy used for suspected sepsis proved to be inappropriate. The outbreak was terminated by temporary closure of NICU in May 1992. Strict hand washing practices were reemphasized, and the previous empiric antibiotic protocol used for suspected sepsis (mezlocillin plus amikacin, and lately ceftazidime plus amikacin) was changed to imipenem and amikacin in the risk population. At closure, 5 additional infants had MRK in stools and/or tracheal suction specimens. Development of MRK organisms should dictate a rational use of empiric antibiotics for neonatal infections in NICU.

Neonatal spinal cord syndrome associated with hypoplastic aortic arch and anemia.

Spinal cord syndrome is a rare postoperative complication in neonates. We describe a case occurring after surgical treatment of a hypoplastic aortic arch in the presence of anemia.

Synchronous mechanical ventilation of the neonate with respiratory disease.

OBJECTIVES: To assess the importance of synchronization of mechanical ventilation with spontaneous respiratory efforts in mechanically ventilated neonates. The actions of this synchronization on ventilation, oxygenation, and BP variation were assessed. DESIGN: Prospective evaluation using within-subject comparison of asynchronous and synchronous states. SETTING: Neonatal ICU in a large, university-affiliated hospital. PATIENTS: Fourteen neonates requiring mechanical ventilation who were initially asynchronous with the ventilator. INTERVENTION: The ventilator settings were adjusted using the patients' own inspiratory and expiratory timing to create synchronous interaction with the ventilator. MEASUREMENTS AND MAIN RESULTS: Synchrony was assessed using clinical observation combined with inspection of the air flow waveform and computerized analysis of the air flow signal to assess cycle-to-cycle reproducibility, so-called autocorrelation. Synchronous ventilation significantly improved tidal volume (p < .05), minute volume (p < .001), and all indices of the variability of arterial BP (p < .001). Mean airway pressure did not change significantly. No infant developed an airleak syndrome or intraventricular hemorrhage, which have previously been associated with asynchronous ventilation and an unstable BP, respectively. CONCLUSION: Synchronous ventilation can be readily applied to most ventilated neonates. It improves ventilation, and results in a marked reduction in BP variation, which may have implications for reducing the risk of intraventricular hemorrhage.

[Psychosocial characteristics of phenylketonuric women: birth defect prevention].

Women with phenylketonuria (PKU) are at high risk for having offspring with mental retardation, microcephaly, heart defects and low birth weight. These adverse outcomes can be prevented by a low-phenylalanine diet started before conception and continued throughout pregnancy. In view of the frequency of poor dietary compliance in women with PKU, a psychosocial model was developed that delineates developmental stages with specific behavioral goals for them to follow. In the present study 15 women with PKU over the age of 16 were followed for 3 years and compared to groups of their healthy acquaintances and of diabetic women. Structured interviews and standard questionnaires were used to study factors hypothesized as being related to the subjects' adjustment and to achievement of their PKU-related behavioral goals. After 1 year most of the PKU subjects were not planning a pregnancy, making their main behavioral goal the prevention of an unplanned pregnancy. Their knowledge of the risks of maternal PKU and family planning was unsatisfactory. PKU subjects had more conservative attitudes about sex and contraception than the controls. The psychosocial profile of PKU subjects pinpointed their special needs and indicated the kinds of specific intervention that might help them adhere to the recommended treatment and prevent birth defects in their offspring.

Murine interleukin-2 generates glycogen-rich and mucus-secreting NK cells.

Colonies of cells termed 'giant granular leucocytes' (GGL) displaying natural killer (NK) activity were generated in cell culture. The prominent feature of these cells was the formation of large cytoplasmic pool--the 'theca'--filled up with glycogen. This was demonstrated by the strong positive red staining of the theca with periodic acid Schiff reagent (PAS) which was abolished by prior treatment with amylase. Two different procedures were employed for obtaining colonies of NK-GGL. In the first, mice were injected either with killed Corynebacterium parvum or with killed Bordetella pertusis preparations and their mesenteric lymph-node cells were grown on syngeneic X-irradiated embryonic skin fibroblast monolayers. At the foci of GGL formation the fibroblasts were killed and the cleared areas thus formed were populated by adherent GGL. In the second procedure, supernates from rat or mouse spleen cultures stimulated with concanavalin A (Con A)--Interleukin-2 (IL-2)--were added to cultures of spleen and lymph-node cells prepared from either ordinary or from athymic nude mice. Richest GGL populations developed when rat IL-2 was added to cells of nude mice. Mouse IL-2 was less consistent. With nude mouse cells it stimulated, either mast cells or GGL, or both; rat IL-2 did not stimulate mast-cell differentiation in nude mouse cultures. In contrast, supernates from lymph-node cell cultures prepared from mice infected with Schistosoma mansoni. Mucosal mast cell-stimulating factor (MMSF) stimulated the formation of colonies of mast cells but not GGL. When MMSF was added as late as 23 days, colonies of young mast cells appeared and mast cells progressively increased in number. When rat IL-2 was added to such mature mast-cell cultures on the 30th day, colonies of cytolytic-GGL appeared. These observations indicate that precursors of mast cells and GGL persist in the cultures and preserve their potential to be stimulated by T-cell factors. GGL-NK cells developed on monolayers prepared from whole embryos released substance that displayed morphology and staining characteristic of mucus. Evidence gathered from in-vitro and in-vivo studies links the in-vitro GGL-NK cells to motile cells that inhabit the mucosal epithelium. Based on the observations, a hypothesis on the function of NK cytotoxicity is brought forward. It proposes the replacement of ordinary epithelial cells, which are killed during a proliferative and differentiative response of other cells at the onset of an infection course.