Multi-Dimensional Laboratory Test Score as a Proxy for Health.

The standard of care for a physician to review laboratory tests results is to weigh each individual laboratory test result and compare it to against a standard reference range. Such a method of scanning can lead to missing high-level information. Different methods have tried to overcome a part of the problem by creating new types of reference values. This research proposes looking at test scores in a higher dimension space. And using machine learning approach, determine whether a subject has abnormal tests result that, according to current practice, would be defined as valid - and thus indicating a possible disease or illness. To determine health status, we look both at a disease-specific level and disease-independent level, while looking at several different outcomes.

A proposed technique for one-step preputial reconstruction in the dog.

OBJECTIVE: To describe a reverse axial pattern flap based on the superficial branch of the dorsal penile artery and describe its use in preputial reconstruction. MATERIALS AND METHODS: Ten penises were harvested from canine cadavers; five were used to describe the dermatome supplied by the superficial branch of the dorsal artery of the penis and five to show perfusion of the skin flap. The superficial branch of the dorsal artery of the penis was identified fluoroscopically by injecting contrast material into the dorsal artery of the penis. This artery was then catheterised and injected with methylene blue to identify the perfused area. A skin flap was created by making a full thickness skin incision at the level of the fornix, along the circumference of the penis. The flap was developed by pulling the cut end toward the tip of the penis while undermining the skin. The flap was considered long enough when the cut end of the flap reached the level of the urethral opening. We also describe a case of preputial resection and reconstruction using this flap. RESULTS: Injection of methylene blue demonstrated the arterial supply to the skin flap. This flap was successful in treating the clinical case following resection of a mast cell tumour on the prepuce, although a small area of full thickness flap necrosis, which healed by second intention, developed postoperatively. CLINICAL IMPORTANCE: This technique may be useful for single step preputial reconstruction.

Repair of lumbosacral fracture-luxation with bilateral twisted string-of-pearls locking plates.

OBJECTIVES: To describe a surgical technique using bilateral twisted string-of-pearls locking plates for lumbosacral fracture-luxation in dogs and cats. MATERIALS AND METHODS: Twisted string-of-pearls locking plates were used to stabilise lumbosacral fracture-luxation between 2013 and 2017. Decompression of the cauda equina was achieved by dorsal laminectomy through a dorso-medial approach. Stabilisation was achieved using bilateral string-of-pearls plates attached to the lateral aspects of the vertebral body cranial to the fractured vertebra and the iliosacral joints. Reduction of the luxation was assessed under fluoroscopy. Outcome and complications were evaluated 24 hours, 6 weeks and 6 months postoperatively. RESULTS: Six animals (four dogs and two cats) were included. Five animals were presented with non-ambulatory paraparesis. Tail anaesthesia and severe lumbosacral pain was evident in all cases but one. Six weeks postoperatively, all animals improved to ambulation, and tail sensation recovered. The long-term clinical outcome was defined as excellent in five and satisfactory in the remaining case. CLINICAL SIGNIFICANCE: Bilateral twisted string-of-pearls locking plates can be associated with a satisfactory result in treating lumbosacral fracture-luxation.

The importance of mRNA structure in determining the pathogenicity of synonymous and non-synonymous mutations in haemophilia.

INTRODUCTION: Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation. However, the role of mRNA structure in determining the pathogenicity of point mutations in haemophilia has not been evaluated. AIM: To evaluate mRNA thermodynamic stability and associated RNA prediction software as a means to distinguish between neutral and disease-associated mutations in haemophilia. METHODS: Five mRNA structure prediction software programs were used to assess the thermodynamic stability of mRNA fragments carrying neutral vs. disease-associated and synonymous vs. non-synonymous point mutations in F8, F9 and a third X-linked gene, DMD (dystrophin). RESULTS: In F8 and DMD, disease-associated mutations tend to occur in more structurally stable mRNA regions, represented by lower MFE (minimum free energy) levels. In comparing multiple software packages for mRNA structure prediction, a 101-151 nucleotide fragment length appears to be a feasible range for structuring future studies. CONCLUSION: mRNA thermodynamic stability is one predictive characteristic, which when combined with other RNA and protein features, may offer significant insight when screening sequencing data for novel disease-associated mutations. Our results also suggest potential utility in evaluating the mRNA thermodynamic stability profile of a gene when determining the viability of interchanging codons for biological and therapeutic applications.

Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.

STUDY QUESTION: Can RNA sequencing of human cumulus cells (CC) reveal molecular pathways involved in the physiology of reproductive aging? STUDY FINDING: Senescent but not young CC activate gene pathways associated with hypoxia and oxidative stress. WHAT IS KNOWN ALREADY: Shifts in socioeconomic norms are resulting in larger numbers of women postponing childbearing. The reproductive potential is sharply decreased with aging, and the reasons are poorly understood. Since CCs play an integral role in oocyte maturation and direct access to human oocytes is limited, we used whole transcriptome analysis of these somatic cells to gain insights into the molecular mechanisms playing a role in follicular senescence. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Twenty CC samples (from a total of 15 patients) were obtained from oocytes of either male factor or egg donor patients. RNA sequencing and bioinformatic tools were used to identify differentially expressed genes between CCs from seven aged and eight young patients (<35 (years old) y.o. vs >40 y.o.). Quantitative-PCR and immunoflourescent staining were used for validation. MAIN RESULTS AND THE ROLE OF CHANCE: RNA sequencing identified 11 572 genes expressed in CC of both age cohorts, 45 of which were differentially expressed. In CC collected from patients >40 y.o., genes involved in the hypoxia stress response (NOS2, RORA and NR4A3), vasculature development (NR2F2, PTHLH), glycolysis (RALGAPA2 and TBC1D4) and cAMP turnover (PDE4D) were significantly overexpressed when compared with CC of patients younger than 35 y.o. LIMITATIONS, REASONS FOR CAUTION: This study focused almost exclusively on assessing the genetic differences in CC transcriptome between young and older women. These genetic findings were not fully correlated with embryonic development and clinical outcome. WIDER IMPLICATIONS OF THE FINDINGS: Our data provide a new hypothesis-follicular hypoxia-as the main mechanism leading to ovarian follicular senescence and suggest a link between cumulus cell aging and oocyte quality decay. If specific molecular findings of hypoxia would be confirmed also in oocytes, genetic platforms could screen CC for hypoxic damage and identify healthier oocytes. Protocols of ovarian stimulation in older patients could also be adjusted to diminish oocyte exposure time to hypoxic follicles. LARGE SCALE DATA: GEO accession number: GSE81579 STUDY FUNDING AND COMPETING INTERESTS: Funded in part by EMD Serono Grant for Fertility Innovation (GFI).

Pemphigus, analysis of 155 patients.

BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. In the last 20 years, immunomodulatory agents have been added to the therapeutic armamentarium. Only few recent studies have evaluated the long-term outcome of pemphigus and possible prognostic parameters in a large group of patients. The aim of this study was to evaluate and analyse the course and prognostic factors of pemphigus in patients followed from 1976 to 2004. PATIENTS AND METHODS: The study group consisted of 155 patients attending the pemphigus clinic of a major tertiary-care medical centre. Background, clinical and treatment data were derived from the patient files and telephone contact. Statistical analysis was performed with Pearson correlation, Fisher exact test, and univariate and multivariate logistic regression models. RESULTS: Age < 40 years at disease onset, Sephardic Jewish origin, and mucosal involvement at diagnosis and high number of relapses were found to be independent prognostic factors of poor outcome. A long (> 1 year) primary remission was a good prognostic factor. During the 26-year study period, 16 patients died. None of the deaths was directly related to either the disease or a complication of treatment. CONCLUSIONS: The course and outcome of pemphigus are worse in patients who are young at diagnosis (< 40 years) or of Sephardic Jewish origin. Mucosal involvement at diagnosis and poor response to treatment also predict poor outcome. The mortality rate of pemphigus is apparently lower than reported in the literature, perhaps because of the contemporary use of adjuvant immunomodulatory therapeutic agents.

Surveillance of childhood vaccine-preventable diseases at health facilities in Jeddah, Saudi Arabia.

A cross-sectional study was conducted at 33 randomly selected health facilities in Jeddah, Saudi Arabia, to assess health facilities' performance and health workers' knowledge of surveillance activities for childhood vaccine-preventable diseases. The WHO surveillance assessment questionnaire and a specially designed knowledge questionnaire were used. There were deficiencies in some surveillance items. The percentages of health facilities that had the surveillance manual and correctly filled clinical registers were 57.6% and 60.6% respectively. In the 6 months preceding the study, 36.4% of facilities lacked the appropriate surveillance forms while only 18.2% had received supervision reviews. Only one-quarter of health workers had a satisfactory knowledge score.

An educational programme on dengue fever prevention and control for females in Jeddah high schools.

A mass communication campaign was conducted at 20 randomly selected female high schools and 2 school supervision centres in Jeddah to improve knowledge, attitudes and practices of students, teachers and supervisors about dengue fever. A total of 5977 pre- and post-intervention questionnaires were completed and the intervention was conducted using lectures and audiovisual aids. A marked improvement in all areas of knowledge, attitudes and practices was observed after the programme in all groups. Students obtained the highest improvement in mean knowledge scores after the programme compared to the other 2 groups. There is a need to expand such programmes to all Jeddah schools.

Severe myopathy mutations modify the nanomechanics of desmin intermediate filaments.

Mutations in the intermediate filament (IF) protein desmin cause severe forms of myofibrillar myopathy characterized by partial aggregation of the extrasarcomeric desmin cytoskeleton and structural disorganization of myofibrils. In contrast to prior expectations, we showed that some of the known disease-causing mutations, such as DesA360P, DesQ389P and DesD399Y, are assembly-competent and do allow formation of bona fide IFs in vitro and in vivo. We also previously demonstrated that atomic force microscopy can be employed to measure the tensile properties of single desmin IFs. Using the same approach on filaments formed by the aforementioned mutant desmins, we now observed two different nanomechanical behaviors: DesA360P exhibited tensile properties similar to that of wild-type desmin IFs, whereas DesQ389P and DesD399Y exhibited local variations in their tensile properties along the filament length. Based on these findings, we hypothesize that DesQ389P and DesD399Y may cause muscle disease by altering the specific biophysical properties of the desmin filaments, thereby compromising both its mechanosensing and mechanotransduction ability.

An educational programme on dengue fever prevention and control for females in Jeddah high schools

A mass communication campaign was conducted at 20 randomly selected female high schools and 2 school supervision centres in Jeddah to improve knowledge, attitudes and practices of students, teachers and supervisors about dengue fever. A total of 5977 pre- and post-intervention questionnaires were completed and the intervention was conducted using lectures and audiovisual aids. A marked improvement in all areas of knowledge, attitudes and practices was observed after the programme in all groups. Students obtained the highest improvement in mean knowledge scores after the programme compared to the other 2 groups. There is a need to expand such programmes to all Jeddah schools

Surveillance of childhood vaccinepreventable diseases at health facilities in Jeddah, Saudi Arabia

A cross-sectional study was conducted at 33 randomly selected health facilities in Jeddah, Saudi Arabia, to assess health facilities' performance and health workers' knowledge of surveillance activities for childhood vaccine-preventable diseases. The WHO surveillance assessment questionnaire and a specially designed knowledge questionnaire were used. There were deficiencies in some surveillance items. The percentages of health facilities that had the surveillance manual and correctly filled clinical registers were 57.6% and 60.6% respectively. In the 6 months preceding the study, 36.4% of facilities lacked the appropriate surveillance forms while only 18.2% had received supervision reviews. Only one-quarter of health workers had a satisfactory knowledge score

Pemphigus--analysis of epidemiological factors in 155 patients.

BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. Only a few studies have evaluated the epidemiological and aetiological parameters of pemphigus vulgaris in a large group of patients over the long term. METHODS: The sample included 155 patients with a diagnosis of pemphigus who attended the pemphigus clinic of a major tertiary medical centre from 1976 to 2004. Data were obtained from the patient files and entered into an ad hoc form; patients were contacted by telephone for missing information. RESULTS: The female-to-male ratio was 1.5 : 1. Non-Ashkenazi Jews accounted for 37% of the sample. In only 10% of the patients was a potential aetiologic or precipitating factor identified. CONCLUSIONS: Pemphigus vulgaris is characterized by a female predominance, consistent with other autoimmune disease. The gender, age and ethnic distribution of affected patients have not changed in the last 40 years. In the vast majority of cases, the aetiologic or precipitating factor is unknown, although drugs appear to be very rare.

Exploring the mechanical behavior of single intermediate filaments.

Intermediate filaments (IFs) are structural elements of eukaryotic cells with distinct mechanical properties. Tissue integrity is severely impaired, in particular in skin and muscle, when IFs are either absent or malfunctioning due to mutations. Our knowledge on the mechanical properties of IFs is mainly based on tensile testing of macroscopic fibers and on the rheology of IF networks. At the single filament level, the only piece of data available is a measure of the persistence length of vimentin IFs. Here, we have employed an atomic force microscopy (AFM) based protocol to directly probe the mechanical properties of single cytoplasmic IFs when adsorbed to a solid support in physiological buffer environment. Three IF types were studied in vitro: recombinant murine desmin, recombinant human keratin K5/K14 and neurofilaments isolated from rat brains, which are composed of the neurofilament triplet proteins NF-L, NF-M and NF-H. Depending on the experimental conditions, the AFM tip was used to laterally displace or to stretch single IFs on the support they had been adsorbed to. Upon applying force, IFs were stretched on average 2.6-fold. The maximum stretching that we encountered was 3.6-fold. A large reduction of the apparent filament diameter was observed concomitantly. The observed mechanical properties therefore suggest that IFs may indeed function as mechanical shock absorbers in vivo.

Competition and cooperation in neuronal processing.

A new type of model neuron is introduced as a building block of an associative memory. The neuron, which has a number of receptor zones, processes both the amplitude and the frequency of input signals, associating a small number of features encoded by those signals. Using this two-parameter input in our model compared to the one-dimensional inputs of conventional model neurons (e.g., the McCulloch Pitts neuron) offers an increased memory capacity. In our model, there is a competition among inputs in each zone with a subsequent cooperation of the winners to specify the output. The associative memory consists of a network of such neurons. A state-space model is used to define the neurodynamics. We explore properties of the neuron and the network and demonstrate its favorable capacity and recall capabilities. Finally, the network is used in an application designed to find trademarks that sound alike.

Outcome of induced labour in pregnancies at 41 weeks gestation and over in Saudi Arabia

A retrospective, descriptive cohort study was conducted at King Faisal Military Hospital, Saudi Arabia, to compare pregnancy outcomes in patients induced with prostagl and in E2 from 41 weeks gestation. A total of 450 women whose antenatal care and delivery were conducted at the hospital during 1995-99 were studied. The main outcome measures used were caesarean section rate and perinatal morbidity and mortality. In otherwise normal pregnancies, the caesarean section rate was not significantly increased when induction of labour was carried out at 41 weeks gestation compared with >/=42 weeks. Although more perinatal complications occurred when induction was carried out at 42 weeks, the results were not statistically significant. A large prospective clinical trial is indicated

Induced labour with prostaglandin E2 in different parity groups after premature rupture of membranes

The study compared the outcome of induction of labour with prostagl and in E2 vaginal tablets in patients with premature rupture of membranes [PROM] at term in different parity groups. A retrospective review was made of the hospital records of 169 women attending the maternity unit of King Faisal Military Hospital, Saudi Arabia. There were no statistically significant differences between the 3 groups [parity 0, parity 1-4 and parity 5+] in rates of labour augmentation, caesarean sections, neonatal intensive care admissions or low Apgar scores. There were no serious complications of induction of labour such as infection or uterine hyperstimulation or rupture. Prostagl and in E2 may be used with care for labour induction in women with PROM at term, even gr and ultiparas, unless there is history of previous caesarean delivery

[Occlusion of the arteries of the fingers after hyperextension trauma]. / Verschluss der Fingerarterien nach Uberstreckungstrauma.

Acute occlusion of digital arteries due to a sport injury A 33 year old female patient with acute ischaemia of the fingers I-II of the right hand was admitted to our emergency unit. She reported that this complete ischaemia had shortly occurred after a sport injury due to an extreme hyperflexion of the right hand in a volleyball match. Four days after this trauma she felt pain and paraesthesia in the right hand. Circular areas of ischaemia were developed with skin colour change to grey and dark blue. The primary measure of the blood pressure by doppler analysis showed no signals in the first and second finger. Initially she received 500 mg Aspirin by intravenous injection. The full therapeutic dose of LMWH related to the weight of the patient was given. On the basis of the short time interval between the occurrence of the symptoms and admission of the patient we decided to perform a so called retrograde intravenous injection. The aim of this therapy was the intraarterial lysis and reperfusion. The blood pressure in all fingers were nearly normal after three days. Daily intravenous transfusion of prostaglandin were given additionally. Necrosis could be prevented as a result of our treatment over seven days. At the end of our therapy only the skin epithelium of the second finger was slightly raised and showed a tendency to desquamation. All other fingers occurred in a normal colour.

A comparison of spontaneous labor with induced vaginal tablets prostaglandin E2 in grand multiparae.

OBJECTIVE: To compare the outcome of labor in grandmultiparous patients (para >5) who had induction of labor with prostaglandin E2 vaginal tablets with grandmultiparous patients in spontaneous labor, and to observe the complications during induction of labor. METHODS: A retrospective case control study was carried out at King Faisal Military Hospital, Khamis Mushayt between January 1993 through until December 1994. This included 64 grandmultiparous patients that were induced with prostaglandin E2 vaginal tablets. Ninety grandmultiparous patients who went into labor spontaneously served as controls. Maternal and fetal data extracted from their hospital record files included age, parity, indication for induction, Bishop score at induction, total dose of prostaglandin used and complications of induction of labor. Other information were length of labor, need for syntocinon augmentation, blood loss during the 3rd stage of labor, mode of delivery, birth weight, sex and Apgar score at 10 minutes. RESULTS: No serious complication of induction of labor such as rupture of the uterus was noted in the subjects studied. There were no significant differences when the mean age and parity of patients in the 2 groups were compared (P>0.05) but there was difference in the gestational age at delivery (p=0.00). There was no significant difference in the mean length of first and 2nd stages of labor. The cesarean section rate was 11% and 8% in the cases and controls, while the need for syntocinon augmentation was twice in the cases than controls, 27% vs 14%. These were not statistically significant. CONCLUSION: We conclude that induction of labor with prostaglandin E2 vaginal tablets may not have adverse effect on the outcome of labor compared with patients in spontaneous labor. It may be safe to use prostaglandin E2 vaginal tablets for induction of labor in the grand- multiparae. We recommend a randomized prospective trial to validate these observations.

Population-based survey of childhood disability in eastern Jeddah using the ten questions tool.

PURPOSE: To identify the prevalence of handicapping disabilities among children up to 15 years of age and their epidemiological pattern in the eastern part of Jeddah. METHODS: In a population-based cross-sectional household survey in the eastern Jeddah area, Saudi Arabia, a multistage sampling method was applied to screen children in 875 houses using the ten questions survey tool for identification of disabilities. Further information collected for detected disabilities included possible risk factors, cause of the disability as perceived by the family and services previously provided to the child. RESULTS: A total of 137 cases of disability were detected giving a point prevalence rate of 36.7 per 1,000 children. Twenty-nine children (21.2%) were discovered for the first time during the survey. The majority of cases were male (57.7%) and the mean age for all cases was 10 years (SD = 5.5) with no case detected under one year of age. Disabled children were in the fourth or fifth birth order among their brothers and sisters and 47 (34%) of them were recorded as a second or third disability in the same family. Number of disabilities in the same child varied widely: 59% of cases had a single disability. 22% had two conditions and 19% had three or more conditions. Speech. motor and mental disabilities ranked top of the disabilities detected by the ten-question tool. The commonest cause of these disabilities as perceived by the family was hereditary diseases followed by childhood illnesses. Significant risk factors associated to these conditions included larger number of children in the family, older age of either parent. histories of handicapping conditions in the original families of either of the parents and presence of handicapping condition in the mothers. Families reported lack of services provided to their disabled children in the community. CONCLUSIONS: The survey tool managed to document. successfully, a prevalence rate of childhood disabilities in the community with a general picture of their types and suspected causes which is quite comparable to that found in Saudi Arabia. It also reported a low service delivery for these disabilities and identified some risk factors related to their occurrence. It is recommended to apply this survey method with certain modifications to suit the local culture in Saudi Arabia. Improvement of the services rendered to handicapped children in Jeddah is also recommended.

Phosphorylation of cytokeratin 8 and 18 in human vascular smooth muscle cells of atherosclerotic lesions and umbilical cord vessels.

Expression of cytokeratins (CK) is considered a hallmark of the state of epithelial differentiation. CK also occur in certain vascular smooth muscle cells (VSMC), inferring an association with a less differentiated phenotype. Recently, CK posttranslational modification was shown to occur in epithelial cells in stress, mitosis or apoptosis. The aim of this study was to determine potential CK phosphorylation patterns in human VSMC. Tissue samples of normal peripheral and coronary arteries, atherosclerotic lesions and umbilical cord vessels were evaluated by immunofluorescence microscopy applying antibodies specific for cytokeratins 8 and 18, specific cytokeratin phosphorylation sites, Ki-67-antigen as a proliferation marker and nick end labeling (TUNEL) to detect apoptosis. All samples contained cytokeratin-positive VSMC but diverse phosphorylation patterns. The C-terminal serine 431 of cytokeratin 8 (CK8Ser-431) was phosphorylated in the vast majority of CK-expressing VSMC of coronary artery lesions. Only a subset of these cells demonstrated phosphorylation of CK18Ser-33 or, to an even lesser extent, CK8Ser-73. DNA fragmentation occurred predominantly in samples containing cells with phosphorylated CK8Ser-431 domains. In contrast, occluded peripheral lesions exhibited little or no phosphorylation. Neonatal VSMC in umbilical cord vessels contain abundant phosphorylated CK domains, again predominantly CK8Ser-431, but also CK18Ser-33. Again, only single cells were found to be proliferating or to contain DNA fragmentation. Thus, abundant CK phosphorylation in VSMC of atherosclerotic lesions suggests a specific functional response to cell stress and a possible relation to apoptosis.