**2. Choice of the target enzyme**

The sequencing of the human genome has promised a revolution in medicine. The genome encodes 20,000- 25,000 human genes, and thousands more proteins as a result of alternative gene splicing. Many of these hold the keys to treating disease, especially numerous enzymes of undefined so far physiologic functions [Gonzaga-Jagureui et al., 2012]. Out of 1200 registered drugs over 300 act as enzyme inhibitors. Most of them are simple analogs of substrates of cer‐ tain enzymatic reaction. Analogy to transition state as a mean to obtain effective inhibitors emerged in 1970s [Lienhard, 1973]. Through the 1970s and 1980s, most of the known examples were natural products [Wolfenden, 1976]. The situation has changed in 1990s when synthetic inhibitors became the predominate examples of transition-state inhibitors. In 1995, there were transition-state analogues for at least 130 enzymes [Radzicka & Wolfenden, 1995].

**Figure 1.** Progress of the enzymatic reaction versus uncatalyzed one.

The design of transition-state inhibitors is likely to become more frequent in the future, alongside with the development of theory and technology for understanding enzyme transi‐ tion states. Today the sequence of information required to obtain transition state analog of enzymatic reaction considers: choice of the suitable enzyme (most likely suited to kinetic isotope effect measurement), selection of presumable mechanism(s) of catalyzed reaction, measurement of kinetic isotope effects (KIE), computer-aided calculations matching the in‐ trinsic KIEs, construction of steric and electronic map of transition state and synthesis of sta‐ ble compound(s) matching this map [Schramm, 2007]. This procedure has been developed gradually in parallel with the advances in KIE enzymology, computational chemistry, and synthetic organic chemistry.


**9. Conclusion**

a bad odor only to mosquitoes but not to people; d) have no effects on clothes; e) be inert to plastics commonly used, such as glasses or bracelets; f)be chemically stable; and g) be eco‐ nomical (Brown & Hebert, 1997). The list of main insect repellents, some of which are also used as insecticides, includes N,N-diethyl-3-methylbenzamide (DEET), permethrin, picari‐ din, indalone, and botanicals (Prato et al., 2012). Additionally, innovative work is in prog‐ ress on the attractiveness of human odors to malaria vectors, with potential applications as mosquito attractants and repellents for use in trapping and personal protection (Zwiebel &

The development of non-chemical strategies alternative to insecticides and repellents is al‐ ready available or currently on study. Before the advent of synthetic insecticides, vector con‐ trol depended primarily on environmental management, and a meta-analysis of data mostly from that period indicated that it substantially reduced malaria risk (Keiser et al., 2005).

Elimination of vector-breeding habitats and managements of water bodies plays a key role in vector suppression, (Walker & Lynch, 2007). In irrigated agriculture, vector breeding can

The role of aquatic predators as control agents of malaria vectors is potentially enhanced through conservation or through the introduction of agents from outside. Larvivorous fish have frequently been reared and released for controlling vector breeding in small water tanks and wells, but successes have generally been limited to more or less permanent water

Microbial larvicides such as *Bacillus thuringiensis israelensis* and *Bacillus sphaericus* produce mosquito-specific toxins associated with a low risk of resistance development (Lacey, 2007). Recent field trials and pilot projects have shown good potential of both bacteria to manage mosquito breeding and to reduce biting rates in certain settings (Fillinger et al., 2008).

Also, insect pathogenic fungi have shown promising results for controlling adult *Anopheles* mosquitoes when sprayed on indoor surfaces and have potential to substantially reduce ma‐

Novel methods under development are genetically engineered mosquitoes and the sterile insect technique (Catteruccia, 2007). Genetic control appears a promising tool, comprising all methods by which a mechanism for pest or vector control is introduced into a wild popula‐ tion through mating. These include the sterile insect release method or the sterile insect tech‐ nique (SIT), through which males are sterilized by irradiation or other means and released to mate with wild females, leading them to lay sterile eggs. Additionally, the introduction of genetic factors into wild populations aimed to make pests harmless to humans might be rel‐

Finally novel approaches against vector borne diseases include transgenesis and paratrans‐ genesis to reduce vector competence (Coutinho-Abreu et al., 2010). For vector transgenesis, the goal is to transform vectors with a gene (or genes) whose protein(s) impair pathogen de‐

be controlled, through land leveling and intermittent irrigation (Keiser et al., 2002).

Takken, 2004).

**8.2. Nonchemical methods**

350 Insecticides - Development of Safer and More Effective Technologies

bodies (Walker & Lynch, 2007).

laria transmission (Scholte et al., 2005).

evant (Pates & Curtis, 2005).

To date, DDT represents a major tool for vector control in areas endemic for malaria, and in 2010 it was the main stay contributing to reduce malaria burden. Despite the big ongoing debate whether improve or ban its use, no convincing evidence on long-term toxic effects of DDT on humans is currently available. In the future, further constructive research aimed at ascertaining DDT effects on human health will be certainly welcome; also, the concurrent use of safe DDT alternatives (as long as they are effective as DDT, of course), should not be neglected. Nevertheless, DDT benefits appear self-evident up to now, thereby justifying its current use as an effective anti-malaria tool.


*<IP_ADDRESS> Orthodontic treatment for osseous defects*

According to the literature, there are three risk groups in a population for progression of periodontal bone loss: (a) those with rapid progression (about 10%), (b) those with moderate progression (the majority, about 80%), and (c) those with no progression (about 10%) [13, 30].

Patients who have had a history with periodontal disease and bone loss, present with no contraindication to receiving orthodontic treatment if the disease has been treated and maintained adequately since. The Periodontist usually guides the Orthodontist in this regard as progression of an untreated periodontal breakdown must be anticipated, however, the patient's periodontal condition must receive attention during planning and execution of orthodontic treatment [30].

#### *<IP_ADDRESS> Hemiseptal defects*

Hemiseptal defects are one-or two-wall osseous defects that are often seen around mesially tipped teeth or supra-erupted teeth. Usually, these defects can be eliminated with orthodontic treatment [30, 31].

Some patients have a discrepancy between both the marginal ridges and the bone levels but these discrepancies may not be of equal magnitude; orthodontic leveling of the bone in this case may not be able to level the marginal ridges. In these patients the crowns of the teeth should not be used as a guide for completing orthodontic therapy. The bone should be leveled, and any remaining discrepancies between the marginal ridges should be equilibrated. In case of a tooth that is tipped, uprighting it will level the defect [31].

If there is supraeruption, then, intrusion and leveling the tooth, can help in leveling the osseous defect. It is important that any periodontal inflammation be controlled before the start of orthodontic therapy. After the completion of orthodontic treatment, these teeth should be stabilized for at least 6 months and reassessed periodontally.

#### *<IP_ADDRESS> Advanced horizontal bone loss*

The location of the bands and brackets on the teeth is a primary determinant of outcome after orthodontic treatment has been planned. In a periodontally healthy individual, the anatomy of the crowns of the teeth determines the position of the brackets. Incisal edges and marginal ridges form a guide to position the anterior brackets and posterior bands or brackets. If the incisal edges and marginal ridges are at the correct level, the cementoenamel junction (CEJ) will also be at the same level. This relationship creates a flat, bony contour between the teeth [13, 32].

In situations where the patient has an underlying periodontal problems and significant alveolar bone loss around certain teeth, using the anatomy of the crown to determine bracket placement is not appropriate. In vital teeth, the equilibration should be performed gradually to allow the pulp to form secondary dentin and insulate the tooth during the equilibration process [32].

The main goal of equilibration and favorable bracket placement is to provide a constructive bony level as well as a more favorable crown-to-root ratio. In some of these patients, the initially apparent periodontal defects may not need periodontal surgery after orthodontic therapy.

#### *<IP_ADDRESS> Furcation defects*

Furcation is the place where the roots of teeth separate. Furcation defect is bone loss, commonly due to a result of periodontal disease affecting the base of the root trunk of a tooth. These furcation defects can be classified as: Class I, Class II and Class III (mild, moderate and severe respectively) [11]. Furcation lesions require special consideration because they are difficult to maintain and can worsen during orthodontic therapy. These patients ideally should be on a 2 to 3 month recall

#### *Orthodontic-Periodontics: An Interdisciplinary Approach DOI: http://dx.doi.org/10.5772/intechopen.98627*

schedule. Detailed instrumentation of the furcation can help minimize further periodontal breakdown.

The treatment modalities in a furcation defect usually involve hemisection (mostly in class III defects). After hemisection, and completion of endodontic and periodontal surgery, can the tooth serve as an abutment. Some molars with class III furcation defects, may have short roots, advanced bone loss, fused roots, or other conditions that contraindicate hemisection. In these patients, extraction and replacement with an implant is advisable [33] at any point irrespective, to the orthodontic treatment.

## *<IP_ADDRESS> Root proximity*

When roots of the posterior teeth are in proximity, periodontal health and restorative options are limited. With the help of orthodontics, these roots can be separated allowing bone to form, which widen the embrasures, provide additional bone support, and make oral hygiene more accessible. The movements should be planned prior to bonding, so they can progress with the initial arch wires. The movements can be monitored with radiographs. A movement of 2-3 mm is usually sufficient for favorable bone response. The oral hygiene maintenance should be good. Occasional occlusal adjustments may be required in the process [31, 33].


**1. Introduction**

Interacting with an assistive or rehabilitation device involves an adaptation of the cognitive and sensorimotor skills of the human being. This fact suggests that a successful development of such a system should imply transdisciplinary studies that consider both technological and psychological issues. **Figure 1** is a systematic representation that describes the phenomena that occur when an individual has to carry out an action mediated through an artefact [1]. Natural mechanisms enable the users to adapt their behaviours to the new situation. Nevertheless, this natural phenomenon presents certain limits and artificial implementations which could be necessary to reduce the gap between the human operator and the machine. The next two sections explain the processes that underlie the natural adaptation

#### **Figure 1.**

*Natural and artificial processes of adaptation that emerge or can be implemented in a context of human-machine interaction.*

happening during the interaction with a tool and how this adaptation can be boosted by technological transformations of the artefact based on an anthropocentric approach.


**3. A four domain clinical model**

A previously published model describes four domains of clinical functioning impacting an individual's adaptive functions. These domains may be scaffolded by family, school, therapeutic, or community supports to improve an individual's adaptive functions. The clinical presentation may manifest as a plethora of externalizing neurobehavioral symptoms masking intrinsic neurodevelopmental deficit. This model can help elucidate the domains of functional deficits to help scaffold the child, adolescent, or young adult with appropriate systems of care to reduce their sensory overstimulation, social pragmatic issues, and/or frustration from neurocognitive issues to minimize outbursts. For example, a child may be having mood outbursts or rage due to hypersensitivity to crowded places (school bus, classroom, playground, lunchroom), people (facial expressions, voice tone, body odor, etc.), sounds (sirens, TV, voice frequency or volume, screechy noises, chalkboard, etc.), smells (food odors, body odor, smoke, decaying trash, sewer, public bathroom, etc.) (**Figure 2**).

**Figure 2.** *Four domain model of neurodevelopmental issues.*

*Perspective Chapter: Autism Spectrum Disorder Neurophenotype with Preconceptional… DOI: http://dx.doi.org/10.5772/intechopen.108820*

### **3.1 Social communication (social intellect)**

Speech and language pragmatics, receptive and expressive language deficits, nonverbal cue recognition, facial expressions, body language, and a variety of other social communication issues can be affected by prenatal alcohol exposure. Social misperceptions, suspiciousness, feeling judged and scrutinized by peers, misunderstanding constructive criticism, personalizing negative comments, over-reacting to social slights are common consequences of the miswiring of neural networks important in social cognition. From an early age, social communication issues are tied to maladaptive attachment behaviors as the individual may lack a social smile, eye contact, and typical attachment behaviors. During early childhood and latency years, these deficits leave the individual vulnerable to social problems and negative peer interactions. By middle school, atypical social interactions leave the adolescent vulnerable to bullying and harassment by peers who misunderstand their social deficits and mood dysregulation or have outpaced them in their social and emotional functioning. Affected individuals' atypical reactions to social slights may cause social disenfranchisement and maladaptive peer interactions (e.g., friends' anger and/or hurt feelings, estrangement from social groups, fear responses in peers, etc.). Often, alexithymia (difficulty recognizing their own emotions and that of others) and poor social perceptions lead family and friends feeling they lack empathy and compassion. Socially awkward facial expressions and nonverbal cues may lead others (e.g., teachers, principals, administrators) to feel they are narcissistic, callous and unemotional. Because of lack of understanding social risk and subtleties of community safety, often these individuals are at risk of having predatory behavior perpetrated against them. Their social dysmaturity makes relationships with younger individuals feel more comfortable, which can lead to inappropriate interactions with peers.

#### **3.2 Neurocognitive (general intellect and executive functions)**

Only 10–15% of individuals affected by prenatal alcohol exposure have intellectual disability (IQ at or below 75 per DSM-5) according to research by the National Institutes on Alcohol Abuse and Alcoholism. Executive functioning issues (organization, planning, time management, working memory, problem solving, visual spatial planning, etc.) are more common sequelae of prenatal alcohol exposure, with attention deficits associated with as little as 1 drink per day or up to 7 drinks per week. Hyperactivity and impulsivity (failure to inhibit unwanted behaviors) lead the individual to be seen as willful and destructive, immature or dysmature, and unable to self-regulate at home, in the classroom, and in the community. These subtle yet important neurodevelopmental functions leave the individual prone to learning challenges, academic failure, vocational problems, and difficulties transitioning into young adulthood. Often, their faulty ego strength masks their challenges, leading to a sense of "false bravado." The resulting subconscious over-inflation of their strengths to hide their challenges can lead the individual to appear haughty, grandiose, narcissistic, and flamboyant. Faulty information processing combined with impulsivity, deficits in consequential thinking and understanding social risk may lead the individual to confabulate, steal, cheat, or be vulnerable to predatory behavior.

#### **3.3 Sensory and motor (sensorium and kinesthetic intellect)**

Our somatosensory, cranial nerves, and voluntary nervous systems are as intricately wired and vulnerable to the effects of prenatal alcohol exposure as our higherlevel brain functions. In fact, the midline brain defects linked to prenatal alcohol exposure from the neural crest cell migration all the way to development of the brain, cranial nerves, somatosensory and motor neurons can be affected by alcohol. Hence, hyper- and hyposensitivities to noise, texture, temperatures, and even interoceptive signals can lead to sensory integration issues. Interoceptive deficits can cause difficulty accurately perceiving signals from the digestive system (e.g., normal digestive sensations from peristalsis, gas, bloating, indigestion, stomach aches, hunger cues), rectum and bladder (defecation and urination signals). These interoceptive signaling issues often lead to emotional outbursts due to lack of understanding of the source of the discomfort and/or frustration/embarrassment due to voiding accidents. Children with interoceptive deficits may have delays in bowel and bladder control, nocturia, fecal smearing (caused by overflow incontinence), somatosensory complaints, and heightened stress response or mood dysregulation caused by hypersensitivities to environmental stimuli.

### **3.4 Emotional regulation (emotional quotient)**

Prenatal alcohol exposure affects the sympathetic and parasympathetic nervous system, leading to emotional dysregulation, autonomic arousal (fight or flight response), sleep–wake cycle disturbances, and a variety of mood problems. Often, affected individuals are irritable, easily frustrated, annoyed, and provoked into heightened stress response by facial expressions, sensory overstimulation, or unpreferred activities. Their emotional dysmaturity leads them to seem years younger than their chronological age, to revert to more primitive mood states during stressful situations, and to be overreactive to discomfort and distress. They are perceived as infants and toddlers as emotionally dysregulated, fussy, hyper-reactive, clingy, and easily fatigued.