The Digital O&P Workshop.

Digitalisation is the megatrend in healthcare, not only since the pandemic. We are two European digital health experts and industry leaders in the field of orthotics and prosthetics (O&P) and in this article we explored what are the underlying trends driving the adoption of digitalisation for customisation of prosthetics & orthotics. We showed that several trends in 3D image capture (input step), 3D modelling (processing step) and 3D printing (output step) currently converge and thus fuel the rapid transformation of the O&P industry. In short outlooks, we rated the probability and timing of adoption rates across the upcoming couple of years. We furthermore reviewed the impact of boundary conditions set by regulators as well as the reimbursement system. Towards the end of this article, we outlined a digital scenario of the near future by following around an orthotist during her work. We finished with a call-to-action targeting regulators, payors, prosthetists/orthotists, and patients to enable such a desirable future.

Importance of the biofilm matrix for the erosion stability of Bacillus subtilis NCIB 3610 biofilms.

Production and secretion of biomolecules can provide new emergent functionalities to the synthesizing organism. In particular, the secretion of extracellular polymeric substances (EPS) by biofilm forming bacteria creates a biofilm matrix that protects the individual bacteria within the biofilm from external stressors such as antibiotics, chemicals and shear flow. Although the main matrix components of biofilms formed by Bacillus subtilis are known, it remains unclear how these matrix components contribute to the erosion stability of B. subtilis biofilms. Here, we combine different biophysical techniques to assess this relation. In particular, we quantify the importance of specific biofilm matrix components on the erosion behavior of biofilms formed by the well-studied Bacillus subtilis NCIB 3610. We find that the absence of biofilm matrix components decreases the erosion stability of NCIB 3610 biofilms in water, largely by abolishing the hydrophobic surface properties of the biofilm and by reducing the biofilm stiffness. However, the erosion resistance of NCIB 3610 biofilms is strongly increased in the presence of metal ions or the antibiotic ciprofloxacin. In the first case, unspecific ionic cross-linking of biofilm components or individual bacteria seems to be responsible for the observed effect, and in the second case there seems to be an unspecific interaction between the antibiotic and the biofilm matrix. Taken together, our results emphasize the importance of the biofilm matrix to reduce biofilm erosion and give insights into how the specific biomolecules interact with certain chemicals to fulfill this task.

Draft Genome Sequence of the Biofilm-Producing Bacillus subtilis Strain B-1, Isolated from an Oil Field.

We report here the draft genome sequence of the Bacillus subtilis strain B-1, a strain known to form biofilms. The biofilm matrix mainly consists of the biopolymer γ-polyglutamate (γ-PGA). The sequence of the genome of this strain allows the study of specific genes involved in biofilm formation.

Carbohydrate coating reduces adhesion of biofilm-forming Bacillus subtilis to gold surfaces.

The growth of bacterial biofilms in pipes and food tanks causes severe problems in industry. Biofilms growing on medical implants or catheters are of great concern, as they can cause serious infections and decrease the functionality of the medical device. The prevention of bacterial adhesion--the first step in colonization and biofilm formation--is therefore very important. Current research comprises alterations in surface properties, the prevention of adhesin biosynthesis, inhibition with receptor analogs, or the development of anti-adhesive vaccines. We present a new approach that allows us to study bacterial adhesion with high sensitivity in real-time while testing several different surfaces in parallel. Using the cantilever-array technique we demonstrate that coating of gold surfaces with mono- or disaccharides results in a reduction of the bacterial adhesion of the biofilm-forming bacterium Bacillus subtilis NCIB 3610 to these gold surfaces. This reduction in bacterial adhesion is independent of the studied carbohydrate. Using several mutant strains, we investigate the underlying molecular interactions, and our results suggest that adhesion to gold surfaces is mediated by thiol groups present in proteins of the bacterial cell membrane or biofilm matrix proteins expressed at low levels by the wild-type strain. Furthermore, our data indicate that the adhesion of B. subtilis NCIB 3610 to carbohydrate-coated gold surfaces is facilitated by interactions between carbohydrates installed on the cantilever gold surface and an exopolysaccharide expressed by this strain. Understanding general and specific contributions of molecular interactions mediating bacterial adhesion will enable its prevention in the future.

Selected metal ions protect Bacillus subtilis biofilms from erosion.

Many problems caused by bacterial biofilms can be traced back to their high resilience towards chemical perturbations and their extraordinary sturdiness towards mechanical forces. However, the molecular mechanisms that link the mechanical properties of a biofilm with the ability of bacteria to survive in different chemical environments remain enigmatic. Here, we study the erosion stability of Bacillus subtilis (B. subtilis) biofilms in the presence of different chemical environments. We find that these biofilms can utilize the absorption of certain metal ions such as Cu(2+), Zn(2+), Fe(2+), Fe(3+) and Al(3+) into the biofilm matrix to avoid erosion by shear forces. Interestingly, many of these metal ions are toxic for planktonic B. subtilis bacteria. However, their toxic activity is suppressed when the ions are absorbed into the biofilm matrix. Our experiments clearly demonstrate that the biofilm matrix has to fulfill a dual function, i.e. regulating both the mechanical properties of the biofilm and providing a selective barrier towards toxic chemicals.

Audio based surveillance forcognitive assistance using a CMT microphone within socially assistive technology.

This work proposes a system for Acoustic Event Detection and Classification (AEDC) using enhanced audio signal provided by a CMT (Coincidence Microphone Technology) microphone. The CMT microphone through signal processing algorithm provides an enhanced signal in several azimuths with a step of 15 degrees . The AEC module exploits this technology to increase classification performance. The automatic detection system based on DWT uses an adaptive threshold for a different energy level and sampling rate quality. The classification system is based on an unsupervised order estimation of Gaussian mixture model adapted to the variability of sound event acoustic information and the representation cost.

Comparison of unreamed nailing and external fixation of tibial diastases--mechanical conditions during healing and biological outcome.

Locked intramedullary nailing and external fixation are alternatives for the stabilization of tibial shaft fractures. The goal of this study was to determine to what extent the mechanical conditions at the fracture site influence the healing process after unreamed tibial nailing compared to external fixation. A standardized tibial diastasis was stabilized with either a locked unreamed tibial nail or a monolateral fixator in a sheep model. Interfragmentary movements and ground reaction parameters were monitored in vivo throughout the healing period. After sacrifice, the tibiae were examined mechanically and histologically. Bending angles and axial torsion at the fracture site were larger in the nail group within the first five weeks post-operatively. Unlike the fixator group, the operated limb in the nail group did not return to full weight bearing during the treatment period. Mechanical and histomorphometrical observations showed significantly inferior bone healing in the nail group compared to the fixator group. In this study, unreamed nailing of a tibial diastasis did not provide rotational stability of the osteosynthesis and resulted in a significant delay in bone healing.

5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.

Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

Increased psychological responses and divergent neuroendocrine responses to m-CPP and ipsapirone in patients with panic disorder.

In patients with panic disorder and /or agoraphobia (PDA) an increased sensitivity of central 5-HT2C receptors and a decreased responsiveness of 5-HT1A receptors has been postulated. In the present study, neuroendocrine challenges were performed using oral doses of the non-selective 5-HT2C agonist m-chlorophenylpiperazine (m-CPP) (0.4 mg/kg), the selective 5-HT1A antagonist ipsapirone (0.3 mg/kg), and placebo in 40 patients with PDA and 12 healthy controls in order to compare 5-HT2C and 5-HT1A-specific psychobehavioural and neuroendocrine response patterns. At baseline, all psychobehavioural variables and the plasma concentration of noradrenaline (NE) were significantly increased in the patient group compared to the controls. The administration of m-CPP or ipsapirone was followed by comparable psychological symptoms and, in 55% of all patients, panic attacks. In comparison to the control subjects, patients were characterized by significantly higher psychological reactions to both challenge agents and a significantly higher NE response to m-CPP. In the patient group, there was also a trend towards an increased cortisol response after administration of m-CPP and a decreased cortisol and hypothermia response after administration of ipsapirone compared to the control group. The neuroendocrine findings of our study support earlier reports of opposite changes in the responsiveness of 5-HT2C and 5-HT1A-related receptors in PDA patients. The behavioural hypersensitivity to both, m-CPP and ipsapiron, shows that the provocation of anxiety and other psychological symptoms might be influenced by

67Ga-citrate and 99Tcm-MDP for estimating the severity of vertebral osteomyelitis.

The aim of this study was to evaluate the roles of 67Ga-citrate and 99Tcm-methylene diphosphonate (99Tcm-MDP) planar and single photon emission tomographic (SPET) imaging in patients with vertebral osteomyelitis. Thirty patients (22 females, 8 males) aged 62.7 +/- 16.4 years (mean +/- s) were enrolled prospectively between May 1995 and May 1998. The patients had been on antibiotics for 7 +/- 4 weeks prior to the study. Histology was available for all but nine patients with mild infections, who were evaluated by a combination of magnetic resonance imaging (MRI), clinical and laboratory tests. 67Ga-citrate (185 MBq) and three-phase bone (555 MBq 99Tcm-MDP) planar and SPET imaging were performed in all patients, together with MRI as a comparison. In total, 67 infectious foci were detected. Based on histology, there were four cases of severe, 13 cases of moderate and four cases of mild osteomyelitis; nine mild infections were also classified by the combination of MRI, clinical and laboratory results. Combined MRI and 67Ga-citrate SPET correctly classified all patients; MRI detected all 67 infectious foci, whereas 67Ga-citrate SPET identified 54 only. False-negative results were seen with all other modalities, especially in cases of mild and moderate infection. 67Ga-citrate SPET identified unsuspected cases of endocarditis (n = 2), paravertebral abscess (n = 1), subaxillary soft tissue abscess (n = 1) and rib osteomyelitis (n = 1). For 67Ga-citrate SPET, the target-to-background ratio was 2.24 +/- 0.31, 1.76 +/- 0.07 and 1.30 +/- 0.18 for severe, moderate and mild osteomyelitis, respectively. Significant differences were noted between severe and moderate infection (P = 0.0051) and between severe and mild infection (P < 0.0001); that between moderate and mild infection was non-significant. For 99Tcm-MDP planar and SPET imaging, and for planar 67Ga-citrate imaging, there was no correlation with severity. We conclude that 67Ga-citrate SPET is able to identify vertebral osteomyelitis and detect additional sites of infection. It can also aid in determining the severity of infection and, potentially, the response to therapy.

Participation of angiotensin receptors in acute hypoxia in mice. II. Effects of angiotensin II nonpeptide receptor ligands losartan (DuP-753) and PD-123319.

The effects of intracerebroventricularly (i.c.v.) administered angiotensin nonpeptide receptor ligands losartan (DuP-753) and PD-123319 and their interactions with Ang II were examined on acute anoxic hypoxia in male mice. Results showed that losartan and PD-123319 exerted antihypoxic effects including increased latency to convulsive seizures and survival time and pretreatment with both drugs enhanced Ang II-increased survival time. Taken together, the results suggest that the antihypoxic effect of losartan and PD-123319 is most likely due to action on brain AT1 and AT2 receptors with both drugs behaving as partial agonists.

Participation of angiotensin receptors in acute hypoxia in mice. I. Effects of angiotensin peptide receptor ligands saralasin and sarmesin.

The effects of angiotensin II (Ang II) and angiotensin receptor ligands sarmesin ([Sar1, Tyr(Me)4] Ang II) and saralasin ([Sar1, Ala8] Ang II) administered intracerebroventricularly (i.c.v.) on acute anoxic hypoxia were studied in mice. The interactions of these ligands and of amastatin (an aminopeptidase A inhibitor) after pretreatment with Ang II and sarmesin, respectively, were also studied. Ang II decreased the latency to hypoxia-induced convulsive seizures and altered survival time (increase or decrease depending on the dose). Sarmesin and saralasin significantly increased the latency to seizures as well as survival time. Pretreatment with saralasin and sarmesin antagonized the Ang II effect on the latency to seizures. Both drugs increased the Ang II effect on the survival time. Amastatin tended to increase the effect of sarmesin on the survival time. Taken together, the results suggest that the antihypoxic effect of sarmesin and saralasin is most likely due to an action on Ang II receptors, with the agents behaving as partial agonists.

Genomic relationships of the North American isolate of infectious salmon anemia virus (ISAV) to the Norwegian strain of ISAV.

Nucleotide and deduced amino acid sequences were determined for a 436 bp reverse transcriptase-polymerase chain reaction (RT-PCR) cDNA fragment from genome segment 8 and a 1151 bp RT-PCR cDNA fragment from genome segment 2 of the North American isolate of infectious salmon anemia virus (ISAV) and compared to the published sequences of Norwegian isolates of ISAV. The North American ISAV isolate exhibited 82.9% identity with the Sotra 92/93 ISAV isolate from Norway in the partial cDNA sequence of genome segment 2, which encodes a polymerase component protein (PB1). The North American ISAV exhibited 88 and 89% identity with 2 partial cDNA sequences of genome segment 8 (nonstructural, NS, gene) reported for the Glesvaer/2/90 isolate from Norway. The North American ISAV exhibited 96.6% similarity with the Sotra 92/93 ISAV isolate from Norway in the deduced amino acid sequences of the PB1 protein. The deduced amino acid sequence of the protein encoded in the partial cDNA fragment of open reading frame (ORF) 1 of genome segment 8 of the North American ISAV exhibited only 71.2 and 66.7% similarity with the 2 sequences of the Norwegian Glesvaer/2/90 isolate. However, the North American ISAV isolate exhibited 96.2 and 87.2% similarity with the 2 sequences of the Norwegian Glesvaer/2/90 isolate in the deduced amino acid sequences of the protein encoded in the partial cDNA of ORF 2. Comparison of these partial cDNA nucleotide and deduced amino acid sequences confirmed that the North American isolate is ISAV. However, the differences observed in these genomic sequences suggest that the North American isolate may represent a distinct genomic variant from the previously described Norwegian strains.

Effects of angiotensin II on biogenic monoamine uptake in the brain of nonhypoxic and hypoxic mice.

The effects of angiotensin II (ATII) administered intacerebroventricularly (i.c.v.) at a dose of 0.5 microgram per mouse on dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) high-affinity uptake in mouse forebrain during hypoxia (asphyxic and hemic) were studied. The influence of hypoxia on biogenic monoamine uptake was also investigated. It was found that DA uptake increased, NA uptake decreased and 5-HT uptake was unchanged after asphyxic hypoxia. Hemic hypoxia had no effect on biogenic monoamine uptake. ATII did not affect uptake of biogenic monoamines in normoxic mice after asphyxic and hemic hypoxia. The results suggest that ATII increases the susceptibility of animals to hypoxia through alterations in the brain high-affinity monoamine uptake.

The mast cell products histamine and serotonin stimulate and TNF-alpha inhibits the proliferation of murine epidermal keratinocytes in situ.

To better characterize the proposed growth modulatory functions of mast cells and their products in the regulation of epidermal homeostasis, we have assessed keratinocyte proliferation by incorporation of [3H]thymidine in murine skin organ cultures after incubation with different concentrations of histamine, serotonin or TNF-alpha. Both histamine and serotonin significantly stimulate the proliferation of keratinocytes as compared to controls (P < 0.001), reaching maxima within a range from micro- to nanomolar concentrations. Even at subnanomolar concentration, TNF-alpha significantly inhibits the incorporation of labelled thymidine by epidermal keratinocytes in murine skin organ culture (P < 0.001). These observations support the concept of mast cell products as modulators of keratinocyte proliferation, and suggest a role for mast cells in the regulation of epidermal tissue turnover under physiological conditions.

[Skin manifestations in leishmaniasis in dogs]. / Hautmanifestationen bei der Leishmaniose des Hundes.

In 23 dogs with clinically apparent leishmaniosis the observed skin lesions were analyzed with respect to appearance, type and localization. The diagnosis could be established in 22 cases by cytological or histological demonstration of the parasite, positive serodiagnosis and typical clinical findings. The following lesions-in order of frequency-were found on the mucous membranes and the skin including foot pads and nails as well as on the mucocutaneous junctions: 1) desquamation with formation of characteristical light scales, 2) localized or symmetrical alopezia, 3) erythema, 4) ulceration and depigmentation was seen especially at the acrae, 5) granulomatous nodules and pustular dermatitis were less common. Hyperkeratosis of the foot pads, onychogriposis and onychorrhexia occurred at the paws. These various cutaneous manifestations of leishmaniosis should be considered in the differential diagnosis of canine skin disease.

[Delusion and sleep deprivation]. / Bouffée délirante et privation de sommeil.

In this article, the authors report two observations of short delusion that occurred after taking Guronsan--a psychostimulant commercialized in France--for a few days, with the intention of maintaining a total deprivation of sleep for three days in both cases. The ensuing clinical picture included a state of depersonalization, a loss of the sense of reality, illusions and even visual hallucinations as well as a delirious feeling of persecution. These disorders altered with the state of vigilance and the patients remembered them clearly. The authors discussed the etiopathogenic role of this psychotrope, as its components--acid ascorbic, glucuronamide and caffein--are not mentioned in literature as causing factors of a psychotic state. Then they compared this psychotrope with other molecules: amphetamines in particular may start a delirium of persecution, but normally they just reveal an underlying psychotic structure, which doesn't seem to be the case here, where the two young adults were only found a little immature. Chloroquine has sometimes been incriminated for disorders similar to those mentioned above, with a difference lying in a greater stability in the duration of these disorders that would persist several days after the end of the treatment. The clinical picture of the two cases was more labile and sedation was complete as soon as the absorption of the psychotrope was interrupted and sleep was restored at the same time. That is why the authors emphasize the importance of the deprivation of sleep as a causing factor of those delusion disorders which have particularly been observed in the case of solitary navigators. The psychiatrist dealing with emergencies shouldn't overlook this clinical and etiological possibility, all the less so as the treatment is simple and the resort to neuroleptics unnecessary.

Effects of angiotensin II on brain monoamines in nonhypoxic and hypoxic mice.

The effects of angiotensin II (ATII) administered intracerebroventricularly (ICV, acute) and subcutaneously (SC, acute and chronic) on acute hypoxia (asphyctic and hemic), and on the forebrain concentrations of monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in male mice were studied. ATII in both routes of administration exerted a decrease of the latency to hypoxia-induced convulsions. ATII slightly reduced the brain levels of DA and NE, and did not change those of 5-HT in hypoxic mice. ATII significantly reduced DA and 5-HT concentrations in nonhypoxic (normoxic) mice. Taken together, the results suggest that ATII-induced increase of susceptibility to hypoxia is accompanied by slight alterations in the brain monoamine metabolism.

Treatment of grade III osteonecrosis of the femoral head with a Charnley/Bicentric hemiarthroplasty.

Thirty-eight hips with Charnley/Bicentric hemiarthroplasties were reviewed. Preoperatively all hips had a Grade III osteonecrosis (Arlet & Ficat) of the femoral head. Follow-up ranged from 42 to 72 months with a mean of 56 months. The mean age was 36 years (range 16-52 years). Three hips with gross loosening of the femoral prosthesis were revised to a cementless total hip replacement: a further two hips exhibited radiological changes indicative of loosening and pending failure. In one hip with progressive loss of joint space and secondary degenerative changes the Bicentric cup was revised to a cemented Charnley component. Acetabular migration was not encountered. Six of 38 hips (15.8%) were thus considered failures. The mean total movement from full abduction to full adduction at the cup-acetabular articulation was 21 degrees, compared to 14 degrees at the inner component articulation. The results of cemented femoral components are predictably unfavourable in this young age group. However, the double articulation of the bipolar cup offers an acceptable method of treatment for this grade of osteonecrosis in the medium term.

[Applied psychoacoustics in space flight]. / Angewandte Psychoakustik im Weltraum.

Simulation free field hearing by head phones by means of digital filter technics was used to investigate directional hearing and audiocinetic vection in microgravity. Our data showed basic informations for the understanding of the reciprocal influence of vestibular and auditory inputs for dynamic orientation. The technical equipment of free field hearing simulation by headphones and the performed experiments are described in detail. Furthermore the new established technology is discussed in terms of the value in psychoacoustic research as well as in clinical practice.